Resources to support your practice
Dosing and administration guide
Step-by-step instructions on how to administer DARZALEX FASPRO® and DARZALEX®.
Patient identification card
ID card informing healthcare providers about treatment with DARZALEX FASPRO® and DARZALEX®.
Daratumumab and serologic testing brochure
Overview of what to know regarding serological testing interference and daratumumab.
Specialty Distributor list
List of Specialty Distributors and their contact information for ordering DARZALEX FASPRO® and DARZALEX®.
DARZALEX FASPRO® administration video
KOL expert series on treating patients with newly diagnosed, transplant-ineligible multiple myeloma
Continuous frontline treatment with DARZALEX® + Rd and patient outcomes
Dr. Suzanne Reim Fanning, Associate Professor at USC School of Medicine Greenville, discusses what the research says about the importance of continuing frontline treatment with DARZALEX® until disease progression or unacceptable toxicity, and how doing so shapes outcomes for patients with multiple myeloma.
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This is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.
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Faculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.
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INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
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In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
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Select Important Safety Information.
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CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.
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Warnings and Precautions: Infusion-Related Reactions
DARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.
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Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
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Additional Important Safety Information will be reviewed later in this video.
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Please see full Prescribing Information available on this website.
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Do you know how important the duration of frontline DRd treatment is for managing patients with newly diagnosed, transplant-ineligible multiple myeloma?
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Hello, I’m Dr. Fanning.
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Join me as we discover why continuous treatment with frontline DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, is a proven path for newly diagnosed patients with transplant-ineligible multiple myeloma.
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Our first topic will cover the importance of frontline treatment in multiple myeloma and why it is an ideal opportunity for achieving deep response. Next, we’ll shift to topics on DARZALEX® treatment, starting with the results of the MAIA trial that studied continuous treatment with frontline DRd versus Rd, or lenalidomide and dexamethasone alone. Once we’ve covered that, we’ll take a closer look at a post hoc subset analysis of DRd and Rd treatment duration and patient outcomes.
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This subset analysis covers patients treated for at least 18 months and we’ll get a better understanding about maintaining treatment benefits with frontline DRd, looking specifically at time to deepest response and safety over time.
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Research demonstrates that the depth of response patients achieve worsens with later lines of therapy. For example, in this retrospective study conducted in 7 European countries, 435 physicians reviewed 4,997 patient charts to map the course of patients with multiple myeloma and to investigate the factors that influence treatment decisions at different stages of the treatment journey. Depth of response, as assessed by the treating physician, was evaluated at each subsequent line of therapy. Profiles of patients with multiple myeloma during the last 12 months were similar across study sites.
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The likelihood of achieving deep response was found to decrease with subsequent lines of treatment for patients with multiple myeloma. The proportion of patients achieving a complete response decreased from 32% at frontline to 4% at fourth line and 2% at fifth line. Similarly, 74% of patients achieved at least a very good partial response with the frontline treatment, compared with only 11% with the fifth line or later. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice. As you can see, frontline treatment is the most appropriate time to aim for deep response compared with later lines of treatment.
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Before we look at the data, let’s get a good understanding of the trial design.
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MAIA was a large, randomized, open-label, multicenter, active-controlled, phase 3 trial that compared DRd vs Rd in a wide range of adult patients with newly diagnosed, transplant-ineligible multiple myeloma. Three hundred sixty-eight patients were randomized to the DRd arm, and three hundred sixty-nine patients were randomized to the Rd arm. Treatment was continued until disease progression or unacceptable toxicity.
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The primary endpoint was progression-free survival.
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Key secondary endpoints included rates of complete response or better, rates of very good partial response or better, rates of minimal residual disease-negativity, overall response rate, overall survival, duration of response, and safety.
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Baseline demographics and disease characteristics were similar between the 2 treatment groups. In the DRd arm, the median age of patients was 73 years. Thirty-four percent had an Eastern Cooperative Oncology Group Performance Status, or ECOG PS, of 0, 50% had an ECOG PS of 1, and 17% had an ECOG PS of 2 or more. Twenty-seven percent had International Staging System, or ISS, Stage I, 43% percent had ISS Stage II, and 29% percent had ISS Stage III disease.
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Now that we have looked at how the MAIA trial was designed, let’s review the primary results of the trial, which showed that frontline DRd significantly reduced the risk of disease progression or death in patients after 28 months of follow-up.
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Median PFS was not reached with DRd vs 31.9 months with Rd alone. The hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. These results were significant, with a P-value of less than 0.0001.
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This translates to a 44% risk reduction for disease progression or death with DRd vs Rd alone.
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The median duration of study treatment was 25.3 months (range 0.1 to 40.44 months) in the DRd group and 21.3 months (range 0.03 to 40.64 months) in the Rd group.
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Now let’s look at long-term progression-free survival.
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After a median follow-up of 64 months, patients were progression-free longer with DRd vs Rd alone.
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The median PFS was 61.9 months with a 95% confidence interval that ranged from 54.8 to not estimable with DRd, versus 34.4 months with a 95% confidence interval that ranged from 29.6 to 39.2 with Rd alone.
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The hazard ratio was 0.55 with a 95% confidence interval that ranged from 0.45 to 0.67.
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This translates to a 45% risk reduction for disease progression or death with DRd vs Rd alone.
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Now, let’s look at the additional efficacy results of overall response rate from the MAIA trial.
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As you can see, a 93% overall response rate was achieved with DRd after a median follow-up of 28 months.
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The median time to response was 1.05 months with DRd with a range from 0.2 to 12.1 months. With Rd the range was from 0.3 to 15.3 months.
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And the median duration of response was not reached with DRd vs 34.7 months with Rd alone, with a 95% confidence interval that ranged from 30.8 to not estimable.
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It is important to note that approximately 50% of patients in the MAIA trial achieved complete response or better with frontline DRd.
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That’s nearly 2 times greater than Rd alone.
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In addition to efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® plus Rd for a median treatment duration of 25.3 months and Rd for 21.3 months, as reported in the primary analysis.
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The most frequently reported adverse reactions were diarrhea, upper respiratory tract infection, infusion-related reactions, constipation, peripheral edema, and fatigue.
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Infusion-related reactions with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion. Most infusion-related reactions occurred during the first infusion.
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Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.
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The most frequently reported hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
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Hematologic abnormalities were more prevalent in the DARZALEX® plus Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® plus Rd arm.
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DARZALEX® can cause severe and/or serious infusion-related reactions, including anaphylactic reactions. In clinical trials (monotherapy and combination: N=2,066), infusion-related reactions, occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3 or 4 infusion-related reaction at Week 2 or subsequent infusions.
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Before we move to our next topic on treatment duration and patient outcomes, let’s consider the case of this hypothetical patient. This is Mindy. Imagine she’s a patient in your practice being treated with frontline therapy. She could be a good candidate for the benefits of maintaining treatment on DRd. Let’s consider her case.
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Mindy’s multiple myeloma was diagnosed 12 months ago following lower back and neck pain and was put on frontline DRd. She was ISS disease stage II and her ECOG PS score was 1. She was also on treatment for early-stage Parkinson’s.
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Given her condition and disease presentation, Mindy was considered ineligible for transplant.
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She is currently continuing her treatment with DRd.
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When you start a patient like Mindy on frontline DRd, are you keeping them on treatment until disease progression or unacceptable toxicity, as was done for patients in the MAIA trial?
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Now, let’s shift our attention to a post hoc subset analysis of treatment duration and patient outcomes.
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It’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.
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Additionally, no conclusions should be drawn. These data should be understood in the context of the methodology.
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Let’s first look at the methodology of this post hoc subset analysis. To explore the impact of treatment duration on long-term clinical outcomes, a post hoc analysis was conducted based on DRd treatment duration (<18 vs 18 months), excluding patients who discontinued therapy due to disease progression during the first 18 months.
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The DRd arm included 283 patients who were treated for at least 18 months, out of 368 patients of the primary intent-to-treat (ITT) analysis of the MAIA trial. The Rd arm included 204 patients, who were treated for at least 18 months, out of 369 patients of the primary ITT analysis of the MAIA trial.
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Response data presented are cumulative deepest response rates achieved by 6, 9, and 18 months for patients who continued all trial treatment for at least 18 months.
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As you can see, more patients achieved complete response or better by 18 months vs 6 months of DARZALEX® + Rd treatment.
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Rates of complete response or better increased over 6, 9, and 18 months of continuous frontline DRd.
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Approximately 50% of patients achieved complete response or better by 18 months of DRd treatment compared with approximately 9% by 6 months of treatment.
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Post hoc subset analysis of the Rd treatment group also showed that more patients achieved complete response or better by 18 months vs 6 months.
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Rates of complete response or better increased over 6, 9, and 18 months of continuous frontline Rd.
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Approximately 30% of patients achieved complete response or better by 18 months of Rd treatment compared with approximately 4% by 6 months of treatment.
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You can see from the results presented that more patients achieved a complete response or better with DRd by 18 months vs Rd alone. Forty-nine point eight percent of the patients receiving DRd achieved complete response or better by 18 months vs 30.4% receiving Rd.
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This post hoc subset analysis shows the increase in complete response rates over 6, 9, and 18 months with continuous frontline DRd.
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Getting back to the hypothetical patient, Mindy, the duration of treatment may be an important consideration for her multiple myeloma treatment.
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If patients like Mindy do not stay on their treatment beyond 6 months, or even 9 months of therapy, they may not experience the benefits achieved by 18 months of therapy.
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Let’s take a closer look at another post hoc subset analysis that evaluated frequently reported adverse events over time for patients who continued their treatment.
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It’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.
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Additionally, no conclusions should be drawn. In the following analysis, treatment-emergent adverse events are presented as observed and should be understood in context with the specific methodology.
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First, let’s review some of the methodology for this analysis. Most frequently reported treatment-emergent adverse events, or TEAEs, that met the threshold of cumulative any-grade greater than or equal to 30%, or Grade 3 or 4 greater than or equal to 10%, are presented here.
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Combined TEAE rates are the sum of the percentages of the most frequently reported events at each cycle period.
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Percentages represent the number of patients with one or more TEAEs by treatment cycle divided by the total number of patients treated within the treatment window.
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Only TEAEs with an onset date falling within the cycle intervals were calculated. Each patient was calculated once per preferred term for each cycle interval. The same patient could be calculated in multiple cycle intervals and for multiple preferred terms. TEAEs may not have resolved by the next cycle.
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Decrease in adverse event rates, or AE rates, over time from treatment initiation was observed for most AEs in both treatment arms. Cataract tended to increase over time in both treatment arms.
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Thirteen percent of intent-to-treat patients discontinued treatment due to a TEAE with DRd vs 22% of the patients with Rd alone.
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In patients who continued treatment, most AE rates decreased over time from treatment initiation to ~30 months for DRd.
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In the Rd arm, patients who continued treatment also experienced decreased AE rates over time from treatment initiation to approximately 30 months.
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You can now see the observed overall AE rates for DRd, which are combined rates of most frequent AEs per treatment cycle.
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When you examine the chart, you can see that in patients who continued treatment, combined rates of frequently reported TEAEs decreased over time from treatment initiation to approximately 30 months for DRd.
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In patients who continued treatment, combined rates of frequently reported TEAEs decreased over time from treatment initiation to approximately 30 months for Rd.
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As an oncologist, you have the opportunity at the time of treatment initiation to set duration of therapy expectations with your patient. This important conversation can help ensure that both you and your patients like Mindy are on the same page in terms of what to expect throughout the course of therapy.
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Before I conclude this video on Advancing Frontline Knowledge and present the summary, I would like to share the Important Safety Information about DARZALEX®.
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IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity. For example, anaphylactic reactions to daratumumab or any of the components of the formulation.
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WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3 or 4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.
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When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
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Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
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To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.
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Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.
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Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test).
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Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.
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Neutropenia and Thrombocytopenia
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
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Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
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Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.
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The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.
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ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.
00:27:47 —> 00:27:55
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:27:56 —> 00:28:09
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
00:28:10 —> 00:28:18
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant.
00:28:19 —> 00:28:27
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant.
00:28:27 —> 00:28:34
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy.
00:28:34 —> 00:28:44
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
00:28:44 —> 00:28:54
In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
00:28:54 —> 00:29:08
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.
00:29:08 —> 00:29:13
Please see full Prescribing Information available on this website.
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In summary, in the treatment of newly diagnosed, transplant-ineligible multiple myeloma, we have seen the benefit of progression-free survival with frontline DRd vs Rd therapy after 28 months and 64 months of follow up.
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We also looked at a post hoc subset analysis of patients who stayed on their treatment for 18 months. We saw that more patients achieved complete response or better at 18 months with DRd and Rd vs 6 months of DRd and Rd.
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For the best chance of achieving progression-free survival seen in the MAIA trial, patients should be treated with DRd until disease progression or unacceptable toxicity.
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Based on this body of evidence from the MAIA trial supporting use of continuous DRd treatment, are you ready to keep your newly diagnosed transplant-ineligible patients on a proven path with DARZALEX® + Rd?
Patient considerations when determining frontline treatment
Dr. Kenneth Shain, Director of the Myeloma Working Group at Moffitt Cancer Center (Tampa, Florida), discusses a typical patient seen in his practice and how he reviews safety and efficacy data along with NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) when choosing a frontline treatment option.
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This is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.
00:00:21 —> 00:00:30
Faculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.
00:00:31 —> 00:00:38
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:00:38 —> 00:00:53
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
00:00:53 —> 00:00:55
Select Important Safety Information.
00:00:55 —> 00:01:09
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.
00:01:10 —> 00:01:25
Warnings and Precautions: Infusion-Related Reactions
DARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.
00:01:26 —> 00:01:57
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
00:01:58 —> 00:02:01
Additional Important Safety Information will be reviewed later in this video.
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DR. SHAIN: I see a broad range of patients with newly diagnosed, transplant-ineligible multiple myeloma in my practice, and I usually spend time taking into account their individual characteristics.
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DR. SHAIN: The question I face is one that you may also encounter—whether the benefits and safety profile of a particular frontline therapy line up with the needs and the medical situation of the patient.
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DR. SHAIN: Hello, I am Dr. Kenneth Shain. Join me, as I discuss a frontline treatment option for newly diagnosed, transplant-ineligible multiple myeloma patients...
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DR. SHAIN:...based on evidence of efficacy and safety results from the MAIA study at 30 months, as well as the follow-up data at approximately 5 years.
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DR. SHAIN: Here is Janice, a patient I typically treat in my practice. She is a 73-year-old retired schoolteacher and a grandmother who was recently diagnosed with multiple myeloma and is not eligible for autologous stem cell transplant. She presented with International Staging System, or ISS, stage II as well as Eastern Cooperative Oncology Group, or ECOG, performance status of 1.
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When considering a frontline treatment option, we need to be thoughtful of her patient characteristics.
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DR. SHAIN: DARZALEX® plus lenalidomide and dexamethasone offers the opportunity for advancing frontline treatment with your patients who are newly diagnosed and transplant-ineligible.
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DR. SHAIN: The MAIA study was a large, randomized, open-label, multicenter, active-controlled phase 3 study of DRd, vs Rd alone.
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DR. SHAIN: The study included 737 adult patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant.
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Patients were randomized, 1 to 1, to either receive DARZALEX® 16 mg/kg by intravenous infusion, weekly for Cycles 1 and 2, every 2 weeks for Cycles 3 through 6, and every 4 weeks for Cycles 7 and beyond, in combination with oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone at 40 mg weekly in the DRd arm; or oral lenalidomide at 25 mg daily, Days 1 through 21, and oral dexamethasone 40 mg weekly, as the active control group: the Rd arm.
00:04:26 —> 00:04:32
Patients in both treatment arms continued until disease progression or unacceptable toxicity.
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DR. SHAIN: The primary endpoint of the study was progression-free survival.
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Key secondary endpoints included a percentage of patients with complete response rate, very good partial response rate, minimal residual disease-negativity rate, overall response rate, overall survival, and of course, safety.
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DR. SHAIN: Let’s first look at the demographics of the patients included in the study.
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The median age was 73 years, with a range of 45 to 90 years in the DRd arm, with 44% of the patients aged 75 years or more.
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In the DRd arm, thirty-four patients, or 35%, had an ECOG performance score of 0, 48% had an ECOG performance score of 1, and 17% had an ECOG performance score of 2 or more.
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Twenty-seven percent of patients had an ISS stage I, 44% had an ISS stage II, and 29% had an ISS stage III disease.
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DR. SHAIN: I am always inclined to look at the data when making a treatment decision for patients who have distinctive needs.
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So, for a patient like Janice let’s see how DRd fits into a frontline treatment.
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DR. SHAIN: The MAIA study reported that DRd demonstrated superior efficacy vs Rd alone.
00:05:46 —> 00:05:52
Let’s first discuss the primary analysis data and then we can get into the approximately 5-year follow-up results.
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As mentioned, progression-free survival was the primary endpoint for the MAIA study. Let’s take a look at the results of this key data point.
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DR. SHAIN: The median progression-free survival for DRd was not reached in the MAIA study, while the median progression-free survival for Rd was 31.9 months.
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The median follow-up was about 30 months. The data reported a hazard ratio of 0.56; with a 95% confidence interval of 0.43 to 0.73, and a p-value of <0.0001.
00:06:27 —> 00:06:34
This amounts to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone.
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DR. SHAIN: At about 30 months, 70.6% of patients had not progressed with DRd vs 55.6% of patients in the Rd group.
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DR. SHAIN: Findings from the MAIA study also demonstrated the impact of the DRd combination regimen on the overall survival in the frontline setting, which was a secondary endpoint.
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DR. SHAIN: In the follow-up analysis at approximately 5 years, MAIA demonstrated an improvement in the overall survival in the DRd arm as compared to the Rd arm. The hazard ratio was 0.68, with a 95% confidence interval of 0.53 to 0.86, and a P-value of 0.0013, representing a 32% reduction in the risk of death in patients treated in the DRd arm. Additionally, median overall survival was not reached for either arm.
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Thus, the evidence presented so far supports choosing frontline DRd to give patients like Janice the opportunity to live longer than with Rd alone.
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DR. SHAIN: Now let’s look at the progression-free survival results for the follow-up analysis at approximately 5 years in the MAIA study.
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It’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.
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Additionally, this analysis was not adjusted for multiplicity and conclusions should not be drawn.
00:07:59 —> 00:08:47
DR. SHAIN: So how does progression-free survival for DRd fare vs Rd alone after about 5 years of follow-up? Median progression-free survival was not reached in the DARZALEX® plus Rd versus 34.4 months with the Rd alone. As you can see, more patients continued living without progression in frontline DRd, with the data showing 53% of patients were progression-free vs 29% for patients on the Rd alone. The hazard ratio was 0.53, with a 95% confidence interval of 0.43 to 0.66, representing a 47% reduction in the risk of disease progression or death with DRd vs Rd alone.
00:08:48 —> 00:08:58
DR. SHAIN: Now let’s take a moment to review the safety profile of DRd reported in the primary analysis as I know it is a key factor when selecting frontline treatment.
00:08:59 —> 00:09:05
In the primary analysis, safety and tolerability were evaluated at a median follow-up of about 30 months.
00:09:06 —> 00:09:32
The most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.
00:09:33 —> 00:09:43
Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.
00:09:44 —> 00:09:52
DR. SHAIN: The most frequent hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
00:09:52 —> 00:10:03
Hematologic abnormalities were more prevalent in the DARZALEX® plus Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® plus Rd arm.
00:10:04 —> 00:10:27
DR. SHAIN: It’s also important to know that in the MAIA trial, infusion-related reactions of any grade with DARZALEX® plus Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification and/or discontinuation of the infusion.
00:10:27 —> 00:10:40
DR. SHAIN: Furthermore, in more than 2000 patients assessed through clinical trials of DARZALEX® as monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions was 37%....
00:10:41 —> 00:10:43
DR. SHAIN:...2% during Week 2 infusions...
00:10:45 —> 00:10:47
DR. SHAIN:...and 6% with subsequent infusions.
00:10:48 —> 00:10:54
DR. SHAIN: Like efficacy, the safety profile of DRd has been continuously evaluated in long-term follow-up analyses.
00:10:55 —> 00:11:09
It’s important to note that treatment-emergent adverse events are reported as observed. Additionally, these analyses are not included in the Prescribing Information and have not been adjusted for multiple comparisons. Therefore, no conclusions should be drawn.
00:11:10 —> 00:11:27
DR. SHAIN: The results show that the safety profile remained similar for DRd in patients over about 5 years of treatment, despite a median treatment duration that was more than twice as long in the DRd group than in the Rd group (47.5 months vs 22.6 months).
00:11:27 —> 00:11:49
The most common grade 3 or 4 treatment-emergent adverse events in more than 15% of patients in either group were neutropenia (54% in the daratumumab group vs 37% of patients in the control group), pneumonia (18% vs 9%), anemia (17% vs 22%), and lymphopenia (16% vs 11%), respectively.
00:11:50 —> 00:12:08
DR. SHAIN: Now, let’s look at the treatment guidelines. According to the NCCN Guidelines, daratumumab in combination with lenalidomide and dexamethasone, is a recommended Category 1 preferred therapeutic option for patients with newly diagnosed, transplant-ineligible multiple myeloma.
MAIA study on frontline treatment with DARZALEX® + Rd vs Rd alone, including primary results, and post hoc analysis in frail patients
Dr. Ruemu Birhiray, the founder of Indy Hematology Review, explores safety and efficacy data of the MAIA trial, including a post hoc analysis in frail patients.
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This is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.
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Faculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.
00:00:31 —> 00:00:38
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:00:38 —> 00:00:53
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
00:00:53 —> 00:00:55
Select Important Safety Information.
00:00:55 —> 00:01:09
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.
00:01:10 —> 00:01:25
Warnings and Precautions: Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.
00:01:26 —> 00:01:57
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
00:01:58 —> 00:02:01
Additional Important Safety Information will be reviewed later in this video.
00:02:02 —> 00:02:22
DR BIRHIRAY:
In the treatment of newly diagnosed, transplant-ineligible multiple myeloma, the benefits of frontline triplet DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs doublet Rd therapy were proven in the MAIA study.
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DR BIRHIRAY:
Hello, I am Dr. Birhiray.
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DR BIRHIRAY:
In this video, I will present primary data from the MAIA study first and then we will look at the post hoc subgroup analysis of the MAIA study in frail patients.
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DR BIRHIRAY:
Before I delve into the results let's spend a moment on the study design of the MAIA study.
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The MAIA study is a large, randomized, open-label, multicenter, active-controlled phase 3 study comparing DRd to Rd alone in a wide range of adult patients with newly diagnosed transplant-ineligible multiple myeloma.
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DR BIRHIRAY:
The study included 737 adult patients with newly diagnosed transplant-ineligible multiple myeloma. Patients were randomized to receive either DRd or Rd alone in 28-day cycles.
00:03:24 —> 00:03:28
The primary endpoint of the study was progression-free survival.
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It's important to point out that treatment was continued until disease progression or unacceptable toxicity.
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DR BIRHIRAY:
Let's take a moment to look at the baseline demographic and disease characteristics included in the study. As you can see, the baseline demographic and disease characteristics were similar between treatment groups. Patients had ECOG performance status scores ranging from 0 to 2. The study also included patients with various ISS disease stage and cytogenetic risk profiles.
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DR BIRHIRAY:
It's important to point out that the median age was 73 years, and it’s worth noting that about 50% were 75 or older.
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DR BIRHIRAY:
So, what were the efficacy and safety results in this broad patient population?
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DR BIRHIRAY:
Let's examine these key findings over here. You can see from the primary results of the MAIA study that the median progression-free survival for DRd was not reached, while the median progression-free survival for Rd was 31.9 months.
00:04:43 —> 00:05:14
DR BIRHIRAY:
The hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. This translates to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone. These results were significant with a P-value of less than 0.0001.
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DR BIRHIRAY:
In addition to efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® + Rd for a median treatment duration of 25.3 months as reported in the primary analysis.
00:05:37 —> 00:06:11
The most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.
00:06:12 —> 00:06:24
DR BIRHIRAY:
Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.
00:06:24 —> 00:06:39
DR BIRHIRAY:
The most frequently reported hematologic laboratory abnormalities for a median treatment duration of 25.3 months were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
00:06:40 —> 00:06:53
Hematologic abnormalities were more prevalent in the DARZALEX® + Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® + Rd arm.
00:06:54 —> 00:07:27
DR BIRHIRAY:
It's also important to know that in the MAIA trial, infusion-related reactions with DARZALEX® plus Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion.
00:07:29 —> 00:07:49
DR BIRHIRAY:
Furthermore, in over 2000 patients assessed through clinical trials of DARZALEX® as a monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions were 37%...
00:07:51 —> 00:07:53
DR BIRHIRAY:
...2% during Week 2 infusions...
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DR BIRHIRAY:
...and 6% with subsequent infusions.
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DR BIRHIRAY:
Let's turn to the post hoc subgroup analysis of the frailty data that I mentioned earlier.
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DR BIRHIRAY:
It's important to consider these analyses are not included in the Prescribing Information for DARZALEX®. These analyses were conducted post hoc and were not adjusted for multiple comparisons. There are insufficient numbers of patients per subgroup to make definitive conclusions of efficacy among the subgroups.
00:08:30 —> 00:08:39
DR BIRHIRAY:
The frailty score was calculated retrospectively using age, Charlson Comorbidity Index, and baseline ECOG performance status score.
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The frailty scores were then used to classify patients into subgroups of fit with a score of 0, intermediate with a score of 1, or frail with a score of 2 or greater.
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Frailty status was further simplified into 2 categories: nonfrail patients with a score of 0 or 1, which was a combination of the fit and intermediate subgroups, and frail patients with a score of greater than or equal to 2. Patients within the nonfrail and frail subgroups were further divided by ISS stage I and II versus III.
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In all, for the DRd arm, there were 196 patients in the nonfrail group and 172 patients in the frail group.
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For the Rd arm alone, there were 200 patients in the nonfrail group and 169 in the frail group.
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DR BIRHIRAY:
Before we go into what a frail patient looks like and the results of this post hoc analysis, let's review some of the limitations of the analysis.
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The retrospective assessment of frailty score was a limitation of this study. Retrospective Charlson Comorbidity Index calculations were based on reported medical history, which may contain missing data and result in underestimating or overestimating the number of patients in each frailty subgroup.
00:10:20 —> 00:10:43
Also, the ECOG performance status score parameter used for frailty score calculations in the study is more subjective, with susceptibility to intra- and inter-observer bias, compared with the activities of daily living and instrumental activities of daily living scales used in the International Myeloma Working Group scoring system.
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DR BIRHIRAY:
Additionally, while the frailty scale used in the study is based on parameters that are routinely assessed in clinical practice for clinical use, the use of comprehensive frailty assessment that more accurately reflect biological or functional frailty will remain important for further optimization of treatment strategies for frail patients.
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Finally, patients with an ECOG performance score of 3 or higher and patients with comorbidities that may interfere with the study procedures were excluded from the MAIA study; the inclusion and exclusion criteria for the study limit the generalizability of these results to more frail patients seen in clinical practice.
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DR BIRHIRAY:
Now that we've established some key considerations regarding the study design, let's discuss what a frail patient may look like in your practice. In my practice, it would be someone like Samuel.
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DR BIRHIRAY:
Samuel is a 78-year-old newly diagnosed, transplant-ineligible multiple myeloma patient. He has an International Staging System, or ISS, disease stage II. His Eastern Cooperative Oncology Group, or ECOG, performance status score is 2.
00:12:09 —> 00:12:13
DR BIRHIRAY:
Additionally, he presented with diabetes and requires assistance to get around.
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DR BIRHIRAY:
Let's see how someone like Samuel aligns with patients on DRd in the post hoc analysis.
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In the DRd frail group, the median age was 77 years, with 51.7% of patients having an ECOG performance score of 1 and 36.6% with an ECOG performance score of 2 or higher.
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DR BIRHIRAY:
It will be of interest to you to know that in a post hoc analysis of the MAIA study, 46.3% of the randomized patients were classified as frail, and 53.7% of patients were classified as nonfrail. Based on these data and frailty assessment criteria discussed earlier, we can agree that Samuel is truly representative of a frail patient seen in the MAIA study.
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DR BIRHIRAY:
I believe you will find these following data interesting when treating patients like Samuel.
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The post hoc subgroup analysis of the MAIA study found that more frail patients had not progressed when adding DARZALEX® to Rd vs Rd alone.
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61.5% of frail patients had not progressed with this frontline triplet regimen versus 39.5% of patients with the doublet regimen.
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DR BIRHIRAY:
The data also showed that in frail patients, there was a 38% reduction in the risk of disease progression or death with DRd vs Rd alone. The hazard ratio was 0.62 and the 95% confidence interval ranged from 0.45 to 0.85.
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DR BIRHIRAY:
Now that we have seen the data of frontline DRd vs Rd alone in frail patients, you are probably asking yourself, what about the safety profile of the frontline triplet therapy in frail patients like Samuel?
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Please note, all treatment-emergent adverse events are reported as observed. These analyses were conducted post-hoc and no conclusions should be drawn.
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The most common Grade 3 and 4 treatment-emergent adverse events in 10% or greater of frail patients included neutropenia, lymphopenia, leukopenia, anemia, thrombocytopenia, infections including pneumonia, cataract, pulmonary embolism, hypokalemia, and hyperglycemia.
00:15:01 —> 00:15:07
Frail patients in the MAIA study had safety results similar to what was seen in the primary analysis of MAIA.
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DR BIRHIRAY:
In addition to the safety data presented in the study, here is some other safety information to consider in older patients across the DARZALEX® clinical trials.
00:15:21 —> 00:15:51
Of the 2459 patients who received DARZALEX® at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older patients than in younger patients.
00:15:52 —> 00:16:25
DR BIRHIRAY:
Among 1213 patients with relapsed and refractory multiple myeloma, the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Among 710 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant, the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.
00:16:26 —> 00:16:33
DR BIRHIRAY:
Before I present the conclusion, I would like to share the Important Safety Information about DARZALEX®.
00:16:34 —> 00:16:36
VOICEOVER:
IMPORTANT SAFETY INFORMATION
00:16:37 —> 00:16:49
CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.
00:16:50 —> 00:18:26
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.
00:18:27 —> 00:19:37
When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, for example 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
00:19:38 —> 00:20:09
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
00:20:10 —> 00:20:37
To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.
00:20:38 —> 00:21:01
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.
00:21:02 —> 00:21:48
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.
00:21:49 —> 00:22:15
Neutropenia and Thrombocytopenia
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
00:22:17 —> 00:22:46
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
00:22:50 —> 00:23:15
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.
00:23:18 —> 00:23:39
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.
00:23:40 —> 00:24:16
ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence 20% or more) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (40% or more) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.
00:24:18 —> 00:24:24
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:24:25 —> 00:24:39
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
00:24:41 —> 00:24:49
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant.
00:24:51 —> 00:25:00
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant.
00:25:01 —> 00:25:06
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy.
00:25:07 —> 00:25:17
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
00:25:19 —> 00:25:29
In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
00:25:30 —> 00:25:43
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.
00:25:44 —> 00:25:48
Please see full Prescribing Information available on this website.
00:25:49 —> 00:26:04
DR BIRHIRAY:
To summarize, the primary results of the MAIA study showed that the median progression-free survival for DRd was not reached, while the median progression-free survival for Rd was 31.9 months.
00:26:06 —> 00:26:38
The most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.
00:26:39 —> 00:26:51
DR BIRHIRAY:
In the post hoc sub-analysis of the MAIA study, frail patients experienced extended progression-free survival with DRd versus Rd alone.
00:26:52 —> 00:26:59
It's important to emphasize that frailty is one consideration when choosing a frontline treatment.
00:27:00 —> 00:27:16
DR BIRHIRAY:
To further this point, the NCCN Guidelines recommend that frailty assessment should be considered for older patients. Given the data I've discussed in this video, I'll leave you with one final thought.
00:27:17 —> 00:27:23
DR BIRHIRAY:
Are you ready to advance the frontline approach with DARZALEX® + Rd?
MAIA study of patients on frontline triplet DARZALEX® + Rd vs Rd alone, along with high-risk subgroup analysis
Dr. Kenneth Shain reviews the efficacy and safety of DRd vs Rd from the MAIA trial, including a subgroup analysis in patients with a high-risk cytogenetic profile.
00:00:14 —> 00:00:21
This is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.
00:00:21 —> 00:00:30
Faculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.
00:00:31 —> 00:00:38
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:00:38 —> 00:00:53
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
00:00:53 —> 00:00:55
Select Important Safety Information
00:00:56 —> 00:01:09
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.
00:01:10 —> 00:01:25
Warnings and Precautions: Infusion-Related Reactions
DARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.
00:01:26 —> 00:01:57
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
00:01:57 —> 00:02:01
Additional Important Safety Information will be reviewed later in this video.
00:02:03 —> 00:02:14
When considering frontline treatment options for newly diagnosed, transplant-ineligible multiple myeloma, evidence from clinical studies that evaluated a range of patient types can be an important factor.
00:02:14 —> 00:02:16
DR. SHAIN: Hello, I am Dr. Kenneth Shain.
00:02:17 —> 00:02:33
DR. SHAIN: We will look at the overall results of the MAIA trial, which studied DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs lenalidomide and dexamethasone, or Rd, alone. Then, we will review data in the high-risk subgroup.
00:02:34 —> 00:02:36
Let’s start with the MAIA study design.
00:02:36 —> 00:02:50
DR. SHAIN: MAIA is a phase 3 global, large, randomized, open-label study comparing DRd vs Rd in a wide range of adult patients with newly diagnosed, transplant-ineligible multiple myeloma.
00:02:50 —> 00:03:49
DR. SHAIN: The study included 737 adult patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant. Patients were randomized, 1 to 1, to receive either DARZALEX® 16 mg/kg by intravenous infusion, weekly for Cycles 1 and 2, every 2 weeks for Cycles 3 through 6, and every 4 weeks for Cycles 7 and beyond, in combination with oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone 40 mg weekly, in the DRd arm; or oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone 40 mg weekly, as the active control group: the Rd arm. Baseline demographic and disease characteristics were similar between treatment groups, and treatment was continued until disease progression or unacceptable toxicity.
00:03:49 —> 00:03:53
DR. SHAIN: In the MAIA study the primary endpoint was progression-free survival.
00:03:53 —> 00:04:09
The key secondary endpoints included greater than or equal to complete response rate, very good partial response rate, minimal residual disease negativity rate, overall response rate, overall survival, duration of response, and safety.
00:04:09 —> 00:04:12
DR. SHAIN: Let’s take a moment to look at the demographics.
00:04:13 —> 00:04:24
In the MAIA study, 17% of the patients in the DRd arm and 16% of the patients in the Rd arm had an Eastern Cooperative Oncology Group performance score of 2 or higher.
00:04:24 —> 00:04:33
29% of the patients in the DRd arm and 30% of the patients in the Rd arm had an International Staging System stage III disease.
00:04:34 —> 00:04:43
Additionally, 15% of the patients in the DRd arm and 14% of the patients in the Rd arm had a high-risk cytogenetic profile.
00:04:44 —> 00:04:49 Median age of patients was 73 years, with a range of 45 to 90 years.
00:04:50 —> 00:04:55
DR. SHAIN: So, what were the primary efficacy and safety results in this broad patient population?
00:04:55 —> 00:05:21
DR. SHAIN: You can see that in the MAIA study, after about 30 months of follow-up, median PFS was not reached with DRd vs 31.9 months with Rd alone. The hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. These results were significant with a P value of less than 0.0001.
00:05:22 —> 00:05:30
DR. SHAIN: This translates to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone.
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At about 30 months, 70.6% of the patients had not progressed with DRd vs 55.6% of the patients in the Rd group.
00:05:42 —> 00:06:02
DR. SHAIN: In addition to the efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® + Rd vs Rd for a median treatment duration of 25.3 months as reported in the primary analysis.
00:06:02 —> 00:06:31
The most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.
00:06:31 —> 00:06:41
Serious adverse reactions with at least 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.
00:06:42 —> 00:06:51
DR. SHAIN: The most frequently reported hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
00:06:51 —> 00:07:03
Hematologic abnormalities were more prevalent in the DARZALEX® + Rd arm compared with the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® + Rd arm.
00:07:03 —> 00:07:24
DR. SHAIN: It’s also important to know that infusion-related reactions, or IRRs, of any grade with DARZALEX® + Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. IRRs of any grade or severity may require management by interruption, modification and/or discontinuation of the infusion.
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DR. SHAIN: Furthermore, in more than 2000 patients assessed through clinical trials of DARZALEX® as a monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions was 37%...
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DR. SHAIN:...2% during Week 2 infusions...
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DR. SHAIN:...and 6% with subsequent infusions.
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DR. SHAIN: Now let’s look at the 5-year follow-up analysis of the MAIA study.
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It is important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA. Additionally, this analysis was not adjusted for multiplicity and conclusions should not be drawn.
00:08:04 —> 00:08:16
DR. SHAIN: At a median follow-up of about 5 years, median progression-free survival was not reached with the DARZALEX® + Rd versus 34.4 months with the Rd alone.
00:08:17 —> 00:08:34
The hazard ratio was 0.53, with a 95% confidence interval that ranged from 0.43 to 0.66. This translates to a 47% reduction in the risk of disease progression or death with DRd versus Rd alone.
00:08:35 —> 00:08:48
DR. SHAIN: Now, let’s look at the 5-year safety analysis. Treatment-emergent adverse events are reported as observed. These analyses have not been adjusted for multiple comparisons, and no conclusions should be drawn.
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Here we can see the most frequent reported treatment-emergent adverse events of any grade in 30% or more and/or Grade 3 or 4 in 10% or more of patients in the DARZALEX® + Rd arm.
00:09:04 —> 00:09:15
The most common treatment-emergent adverse events of Grade 3 or higher in 15% or more of patients in either group were neutropenia, pneumonia, anemia, and lymphopenia.
00:09:15 —> 00:09:21
The safety profile remained similar for DRd over approximately 5 years of treatment.
00:09:22 —> 00:09:40
DR. SHAIN: The results show that the safety profile remained similar for DRd in patients over about 5 years of treatment, despite a median treatment duration that was more than twice as long as the DRd group than in the Rd group (47.5 months vs 22.6 months).
00:09:41 —> 00:10:05
The most common grade 3 or 4 treatment-emergent adverse events in more than 15% of patients in either group were neutropenia, 54% in the daratumumab group vs 37% of patients in the control group; pneumonia, 18% vs 9%; anemia, 17% vs 22%; and lymphopenia, 16% vs 11%, respectively.
00:10:05 —> 00:10:13
DR. SHAIN: Cumulative Grade 3/4 infection rates were 41% for DRd vs 29% for Rd alone.
00:10:14 —> 00:10:23
The cumulative rates of discontinuation due to treatment-emergent adverse events were 13% for the DRd group and 22% for the Rd group.
00:10:24 —> 00:10:37
DR. SHAIN: We just reviewed the primary and follow-up efficacy and safety data. I will now present 3-year and 5-year subgroup analyses that further examine the efficacy of DRd in the various patient types I mentioned earlier.
00:10:37 —> 00:10:56
It is important to note that these analyses are not included in the Prescribing Information for DARZALEX®. Additionally, the high-risk subgroup analyses were prespecified and not post hoc. There are insufficient numbers of patients per subgroup to make definitive conclusions of efficacy among the subgroups.
00:10:57 —> 00:11:00
DR. SHAIN: Now let’s turn to the subgroup analysis.
00:11:01 —> 00:11:13
Follow-up subgroup analyses of progression-free survival were conducted at around 3 years and around 5 years in various subpopulations, including patients with high-risk cytogenetic profile.
00:11:13 —> 00:11:32
DR. SHAIN: Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotypic analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality: 17p deletion, 14,16 translocation, or 4,14 translocations.
00:11:32 —> 00:11:40
DR. SHAIN: What does a high-risk patient look like? Let’s take a look at a hypothetical patient I may see in my practice. It would be someone like Luis.
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DR. SHAIN: Luis is 76 years old and reported severe lumbar pain.
00:11:45 —> 00:11:55
He underwent a workup that established a diagnosis of high-risk multiple myeloma, of International Staging System stage III with the presence of high-risk cytogenetics.
00:11:56 —> 00:12:01
Given his age and his comorbidities, he was determined to be transplant ineligible.
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DR. SHAIN: How often do you come across patients who are high risk? It may be more common than we think.
00:12:08 —> 00:12:13
Nearly 15% of patients with newly diagnosed multiple myeloma are considered high risk.
00:12:14 —> 00:12:26
DR. SHAIN: Given that these patients can be difficult to treat due to the aggressive nature of their disease and the high risk of progression, considering a frontline treatment that is effective becomes a priority.
00:12:27 —> 00:12:33
DR. SHAIN: Let’s examine the subgroup analysis of the MAIA study in a broad range of patient types, including high-risk patients.
00:12:34 —> 00:12:37
DR. SHAIN: Now, let’s dive into the data a bit deeper.
00:12:38 —> 00:12:48
DR. SHAIN: Note, in the subgroup analysis at approximately 3 years, PFS numerically favored DARZALEX® + Rd in most subgroups vs Rd alone.
00:12:48 —> 00:13:02
DR. SHAIN: And when we examine the subgroup follow-up at about 5 years, progression-free survival continued to numerically favor patients on frontline DARZALEX® + Rd vs Rd alone, including high-risk patients like Luis.
00:13:03 —> 00:13:04
DR. SHAIN: Now, let’s look at the 5-year data.
00:13:05 —> 00:13:25
DR. SHAIN: In high-risk patients, at about 3 years, median progression-free survival, or median PFS, was not reached with both DRd and Rd alone, and at about 5 years, median PFS was 45.3 months with the DRd vs 29.6 months with Rd alone.
00:13:26 —> 00:13:35
DR. SHAIN: Before I share the Important Safety Information for DARZALEX® and conclude the video, I wanted to reiterate a few key points from the MAIA study we just discussed.
00:13:35 —> 00:13:44
First, the primary results demonstrate progression-free survival benefit for frontline triplet DARZALEX® plus Rd vs doublet Rd.
00:13:44 —> 00:13:57
Second, progression-free survival continued to numerically favor DRd in our review of the follow-ups at approximately 3 years and 5 years, both of which included high-risk patients.
00:13:58 —> 00:14:02
Now let’s review the Important Safety Information and Indications for DARZALEX®.
00:14:03 —> 00:14:17
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity; for example, anaphylactic reactions to daratumumab or any of the components of the formulation.
00:14:19 —> 00:15:55
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.
00:15:56 —> 00:17:05
When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days; for example, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
00:17:06 —> 00:17:38
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
00:17:39 —> 00:18:05
To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.
00:18:06 —> 00:18:29
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.
00:18:31 —> 00:19:16
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.
00:19:17 —> 00:19:44
Neutropenia and Thrombocytopenia
DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.
00:19:45 —> 00:20:15
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
00:20:19 —> 00:20:45
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.
00:20:47 —> 00:21:07
The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. 00:21:09 —> 00:21:45
ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.
00:21:46 —> 00:21:53
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
00:21:54 —> 00:22:07
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
00:22:09 —> 00:22:18
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
00:22:20 —> 00:22:28
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
00:22:29 —> 00:22:35
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
00:22:36 —> 00:22:46
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
00:22:48 —> 00:22:57
In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
00:22:58 —> 00:23:12
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
00:23:12 —> 00:23:16
Please see full Prescribing Information available on this website.
00:23:17 —> 00:23:42
DR. SHAIN: In conclusion, what we have seen from the MAIA study is that in the treatment of newly diagnosed, transplant-ineligible multiple myeloma, the progression-free survival benefits of frontline triplet DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs doublet Rd therapy were demonstrated at approximately 3 years, with additional follow-up at about 5 years.
00:23:43 —> 00:23:50
DR. SHAIN: In addition to the progression-free survival benefits, we also looked at available long-term data for subgroups of patients who are at high risk.
00:23:51 —> 00:24:03
DR. SHAIN: Based on the data that I have presented from the MAIA trial, are you ready to advance the frontline approach with DRd in your appropriate transplant-ineligible multiple myeloma patients?
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); KOL=key opinion leader; Rd=lenalidomide (R) + dexamethasone (d).
Once you have made the clinical decision to prescribe DARZALEX®, Johnson & Johnson has resources to help you support your patients.
J&J withMe is your single source for access, affordability, and treatment support programs from Johnson & Johnson. Your patients will be connected to DARZALEX withMe.
- Access support to help navigate payer processes
- Affordability resources to help patients discover ways to afford their DARZALEX®
or DARZALEX FASPRO® medicine - Dedicated, free 1-on-1 Care Navigator support for your patients —offered through DARZALEX withMe — to support the nonclinical needs that may arise while on DARZALEX® or
DARZALEX FASPRO®
- Visit Portal.JNJwithMe.com to investigate insurance coverage for your patients, enroll your patients in savings, or sign them up for Care Navigator support
- Visit JNJwithMe.com/hcp/ for access and affordability information for the J&J medicine you prescribed
- Bookmark these links for quick and easy access!
- Questions? Call 833-JNJ-wMe1 (833-565-9631), Monday through Friday, 8:00 AM to 8:00 PM ET
Get your patients connected to J&J withMe support by asking them to enroll at DarzalexwithMe.com.
The patient support and resources provided by J&J withMe and DARZALEX withMe are not intended to provide medical advice, replace a treatment plan from the patient’s doctor or nurse, provide case management services, or serve as a reason to prescribe DARZALEX® or DARZALEX FASPRO®.
Helpful tools you can share with your patients and their caregivers
Conversation starter guide
A tally of questions related to DARZALEX FASPRO® treatment that patients can choose from to discuss with their healthcare team.
Customized conversation starter
Interactive tool that allows patients to create a list of questions for discussion with their healthcare team on topics relevant to their condition and DARZALEX FASPRO® treatment.
Dosing calendar
Helps your patients stay on track with their DARZALEX FASPRO® treatment regimen.
Customized dosing calendar
Interactive tool patients can use to generate dosing calendars for their DARZALEX FASPRO® regimen.
Patient website
Comprehensive resource dedicated to educating and supporting patients with multiple myeloma and their caregivers.
What to expect guide
Help your patients understand what will happen before, during, and after treatment with
DARZALEX FASPRO®
Real stories from real patients
Let your patients explore how other patients
share their treatment experiences with
DARZALEX FASPRO®
Education and support groups
A list of organizations that provide education and support to patients with multiple myeloma.
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Questions & answers
DARZALEX FASPRO® is indicated for the treatment of adult patients with newly diagnosed multiple myeloma:
- Transplant-eligible—in combination with VRd1
- Transplant-ineligible—in combination with Rd and in combination with VMP1
DARZALEX® is indicated for the treatment of transplant-ineligible, adult patients with newly diagnosed multiple myeloma—in combination with Rd and in combination with VMP2
Rd=lenalidomide (R) + dexamethasone (d); VMP=bortezomib (V) + melphalan (M) + prednisone (P); VRd=bortezomib (V), lenalidomide (R), and dexamethasone (d).
Daratumumab* (D) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) is recommended by the NCCN Guidelines as a Category 1 preferred† therapeutic option for newly diagnosed, transplant-ineligible multiple myeloma.‡ Daratumumab and hyaluronidase-fihj + VRd is indicated for induction and consolidation in newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant.
Daratumumab* (D) in combination with lenalidomide, and dexamethasone (Rd) is recommended by the NCCN Guidelines as a Category 1 preferred† therapeutic option for newly diagnosed, transplant-ineligible multiple myeloma.‡
*Daratumumab includes daratumumab and hyaluronidase-fihj (DARZALEX FASPRO®) for subcutaneous injection and daratumumab (DARZALEX®) for intravenous infusion. Daratumumab and hyaluronidase-fihj for subcutaneous injection has different dosing and administration instructions compared to daratumumab for intravenous infusion.
†See NCCN.org for definitions of NCCN Categories of Preference and NCCN Categories of Evidence and Consensus.
‡Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed October 11, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
DARZALEX FASPRO® is the only anti-CD38 monoclonal antibody that can be delivered subcutaneously in ~3 to 5 minutes1-3
For adult patients who have newly diagnosed, transplant-ineligible multiple myeloma and are being treated with DRd, dosing frequency decreases to once every 4 weeks starting at Cycle 7.1,2
DRd=DARZALEX®/DARZALEX FASPRO® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
In the COLUMBA trial, nearly 3x reduction in systemic ARRs with DARZALEX FASPRO® (13%, n=260) vs DARZALEX® (34%, n=258) was observed.1
Both systemic ARRs, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.1
The PERSEUS trial was a Phase 3, open-label, randomized, active-controlled trial in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplant (ASCT), comparing DARZALEX FASPRO® + VRd (n=355) vs VRd (n=354) during induction and consolidation. The major efficacy outcome measure was progression-free survival (PFS) by Independent Review Committee (IRC) assessment based on International Myeloma Working Group (IMWG) response criteria. The median age was 60 years (range: 31-70)2,4
Following post-transplant consolidation, patients received investigational DR maintenance vs R alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in maintenance, and the efficacy of DR for maintenance has not been established.
The primary efficacy endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR) and minimal residual disease (MRD).4
DR=DARZALEX® (D) + lenalidomide (R); VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
The efficacy of DVRd was evaluated in the PERSEUS trial, a phase 3, global, randomized, open-label trial comparing treatment with DVRd (n=355) to VRd (n=354) in adult patients with newly diagnosed, transplant-eligible multiple myeloma. In the trial, treatment was continued until disease progression or unacceptable toxicity.2,4
Following post-transplant consolidation, patients received investigational DR maintenance vs R alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in maintenance, and the efficacy of DR for maintenance has not been established.
After 47.5 months of follow-up, there was a 60% reduction in the risk of disease progression or death with DVRd vs VRd alone (HR=0.40; 95% CI: 0.29-0.57; P<0.0001).4*†
CI=confidence interval; DVRd=DARZALEX® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NR=not reached; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Median follow-up was 47.5 months in the DVRd and VRd group (range: 0.0-54.4 months).4
†Progression-free survival was by IRC assessment based on IMWG criteria.2
The efficacy of DRd was evaluated in the MAIA trial, a phase 3, global, randomized, open-label trial, comparing treatment with DRd (n=368) to Rd (n=369) in adult patients with newly diagnosed, transplant-ineligible multiple myeloma. In the trial, treatment was continued until disease progression or unacceptable toxicity.2,3,5
The primary efficacy endpoint was progression-free survival (PFS). One of the secondary endpoints was overall survival (OS).2
After 28 months of follow-up, there was a 44% reduction in the risk of disease progression or death with DRd vs Rd alone (HR=0.56; 95% CI: 0.43, 0.73; P<0.0001).2.
After 64 months of follow-up, median PFS was 61.9 months (95% CI: 54.8-NE) with DRd vs 34.4 months (95% CI: 29.6-39.2) with Rd (HR=0.55; 95% CI: 0.45, 0.67).
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NE=not estimable; Rd=lenalidomide (R) + dexamethasone (d).
In the MAIA trial, DRd was evaluated in a wide range of patients. About 50% of patients were 75 years of age or older and the trial included patients with various ECOG performance status, cytogenetic profiles, and ISS disease stages.2,6
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG=Eastern Cooperative Oncology Group; ISS=International Staging System.
DRd is indicated for the treatment of newly diagnosed, transplant-ineligible multiple myeloma until progression or unacceptable toxicity. For the best chance of achieving the PFS and sustained responses seen in the MAIA trial, patients should be treated with DRd until progression or unacceptable toxicity.2
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); PFS=progression-free survival.
DARZALEX FASPRO® and DARZALEX® are covered for ~97% of people with commercial insurance and ~97% of people with Medicare.7
This may not represent 100% of lives due to data limitations.
Daratumumab inhibits tumor cell growth through immune-mediated, direct on-tumor, and immunoregulatory actions. It may also have an effect on normal cells.1
There are a wide variety of resources available to help provide educational, emotional, and financial support to patients throughout their treatment.
Your patients have access to free 1-on-1 support from a dedicated Care Navigator* who can help them:
- Understand their disease and learn more about DARZALEX® or DARZALEX FASPRO®
- Find health and wellness resources for living with cancer
- Explore cost support options regardless of their insurance type
- Help them find online or in-person patient-to-patient support
- Connect them with transportation-related services in their community
Get started with J&J withMe
- Visit Portal.JNJwithMe.com to investigate insurance coverage for your patients, enroll your patients in savings, or sign them up for Care Navigator support
- Visit JNJwithMe.com/hcp/ for access and affordability information for DARZALEX® and DARZALEX FASPRO®
- Questions? Call 833-JNJ-wMe1 (833-565-9631), Monday through Friday, 8:00 AM to 8:00 PM ET.
*Care Navigators do not provide medical advice.