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MAIA trial demonstrated the efficacy and safety of frontline DARZALEX® + Rd in newly diagnosed, transplant-ineligible multiple myeloma1
Featuring clinical results at 28 months and ~5 years
A large, randomized, open-label, multicenter, active-controlled phase 3 trial1
BMI=body mass index; DRd=DARZALEX ® (D) + lenalidomide (R) + dexamethasone (d); ECOG=Eastern Cooperative Oncology Group; IV=intravenous; PD=progressive disease; PO=by mouth; QW=weekly; Q2W=every 2 weeks; Q4W=every 4 weeks; Rd=lenalidomide (R) + dexamethasone (d).
*On days when daratumumab was administered, dexamethasone was administered to patients in the DRd arm and served as the treatment dose of steroid for that day, as well as the required pre-infusion medication.1
†For patients older than 75 years of age or with BMI <18.5, dexamethasone was administered at a dose of 20 mg weekly.1
Primary endpoint was progression-free survival (PFS).2‡
Key secondary endpoints included: percentage of patients with complete response (CR) rate, very good partial response (VGPR) rate, minimal residual disease (MRD)-negativity rate (next-generation sequencing [NGS]; 10-5), overall response rate (ORR), overall survival (OS), duration of response, and safety.2
Baseline demographics and disease characteristics were similar between the 2 treatment groups.1
‡Efficacy was evaluated by PFS (based on International Myeloma Working Group [IMWG] criteria).2
MAIA trial evaluated a wide range of newly diagnosed, transplant-ineligible patients, including elderly, poor performance status, and high cytogenetic risk patients2,3
ECOG=Eastern Cooperative Oncology Group; ISS=International Staging System; Rd=lenalidomide (R) + dexamethasone (d).
*Per protocol, cytogenetic tests from bone marrow aspirates were performed by local laboratories at screening, and 642 patients had baseline cytogenetic data reported from local laboratories out of the 737 patients who were enrolled in MAIA.4,5
†Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotype analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality (del17p, t[14;16], or t[4;14]).2
- ~50% of patients were 75 years old or older2
- The trial also included patients with various Eastern Cooperative Oncology Group (ECOG) performance status, cytogenetic profiles, and International Staging System (ISS) disease stages2
Clinical results for frail and high-risk patient subgroups
National Comprehensive Cancer Network® (NCCN®) Category 1, preferred
Daratumumab* (D) in combination with lenalidomide (R) and dexamethasone (d) is recommended by the NCCN Guidelines as a Category 1 preferred† therapeutic option for patients with newly diagnosed, transplant-ineligible multiple myeloma‡
*Daratumumab includes both 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 V3.2023.
© National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed December 12, 2022. To view the most recent and complete version of the guideline, go online to www.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.
Powerful efficacy to start the treatment journey
Frontline DARZALEX® + Rd significantly reduced the risk of progression in patients after 28 months of follow-up1*
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NE=not estimable; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
*Median follow-up was 28 months (range: 0.0-41.4 months).2
†Kaplan-Meier estimate.2
At 30 months: 70.6% of patients had not progressed with DRd vs 55.6% of patients in the Rd group (DRd: 95% CI: 65.0, 75.4; Rd: 95% CI: 49.5, 61.3)2†
After 64 months, 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 alone1‡
‡Median follow-up was 64 months.1
After 28 months of follow-up:Deep responses for a strong start. Durable responses to keep your patients' treatment journeys moving forward1*
CR=complete response; ORR=overall response rate; PR=partial response; Rd=lenalidomide (R) + dexamethasone (d); sCR=stringent complete response; VGPR=very good partial response.
*Median follow-up was 28 months (range: 0.0-41.4 months).2
‡sCR is CR plus normal free light chain ratio and the absence of clonal cells in bone marrow as assessed by immunohistochemistry or immunofluorescence.2
93% overall response rate (ORR) was achieved with DARZALEX® + Rd after 28 months of follow-up.1*
DEPTH1
- DRd nearly doubled the number of patients who achieved complete response (CR) or better vs Rd alone
— More than doubled stringent complete response‡ (sCR): 30% with DRd vs 13% with Rd alone
DURABILITY1
- Median duration of response has not yet been reached with DRd vs 34.7 months (95% CI: 30.8, not estimable) for Rd alone
SPEED OF RESPONSE1
- Median time to response was 1.05 months with DRd (range: 0.2–12.1 months) and with Rd alone (range: 0.3–15.3 months)
After 28 months of follow-up:Patients experienced MRD negativity with frontline DARZALEX® + Rd at a rate 3x greater than Rd alone1*†
3.4x greater MRD negativity with DRd1
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); MRD=minimal residual disease; Rd=lenalidomide (R) + dexamethasone (d).
Superior minimal residual disease (MRD) rates vs Rd alone after 28 months of follow-up.1
- 24% of patients were MRD negative with DRd (95% CI: 19.9, 28.9)1
- 7% of patients were MRD negative with Rd (95% CI: 4.9, 10.5)1
MRD was based on a sensitivity threshold of 10-5 using a next-generation sequencing assay (ClonoSEQ).1,2
*Median follow-up was 28 months (range: 0.0-41.4 months).2
†MRD negativity was defined as undetectable levels of multiple myeloma cells by bone marrow aspirate at any time point after the randomization and before disease progression or start of subsequent therapy, and in the trial was assessed by means of next-generation sequencing assay at a sensitivity threshold of 10-5 via bone marrow aspirate, collected at initial trial screening, at the time of confirmation of complete response or stringent complete response, and thereafter at 12, 18, 24, and 30 months.2
After 56 months of follow-up:Frontline DARZALEX® + Rd significantly reduced the risk of death vs Rd alone1*
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; IQR=interquartile range; OS=overall survival; Rd=lenalidomide (R) + dexamethasone (d).
*Median follow-up was 56 months in the DRd group (IQR: 53.0-60.1 months) and in the Rd group (IQR: 52.5-59.4 months).1,3
†Kaplan-Meier estimate.3
At 60 months: 66% of patients were still alive with DARZALEX® + Rd vs 53% with Rd alone (DRd, 95% CI: 61, 71; Rd, 95% CI: 47, 59)3†
After 64 months of follow-up:More patients continued living without progression with frontline DARZALEX® + Rd1*
Median PFS was 61.9 months (95% CI: 54.8, NE) in the DRd arm and 34.4 months (95% CI: 29.6, 39.2) in the Rd arm1
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NE=not evaluable; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
*Median follow-up was 64 months.1
You are now viewing a follow-up analysis of the MAIA study. This information is not included in the current Prescribing Information and has not been evaluated by the FDA.
Cumulative response rates after 56 months of follow-up1,3*
CR=complete response; IQR=interquartile range; ORR=overall response rate; PR=partial response; Rd=lenalidomide (R) + dexamethasone (d); sCR=stringent complete response; VGPR=very good partial response.
*Median follow-up was 56 months in the DRd group (IQR: 53.0-60.1) and in the Rd group (IQR: 52.5-59.4).1,3
‡sCR is CR plus normal free light chain ratio and the absence of clonal cells in bone marrow as assessed by immunohistochemistry or immunofluorescence.2
93% overall response rate (ORR) was achieved with DARZALEX® + Rd after 56 months of follow-up.3
DEPTH3
- 1.7x more patients receiving DRd achieved complete response (CR) or better vs Rd alone
— More than doubled stringent complete response† (sCR): 35% with DRd vs 15% with Rd alone
DURABILITY3
- Median duration of response was not reached with DRd vs 43.9 months (95% CI: 37.7, 52.9) for Rd alone
The follow-up analysis was not adjusted for multiplicity and conclusions should not be drawn.
Demonstrated safety profile of frontline triplet therapy with DRd
Frontline DARZALEX® + Rd provides a demonstrated safety profile for your patients1*
Most frequent adverse reactions reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Rd arm1*†
Adverse reactions reported in primary analysis
Rd=lenalidomide (R) + dexamethasone (d).
*Median duration of study treatment was 25.3 months (range: 0.1–40.44 months) in the DRd group and 21.3 months (range: 0.03–40.64 months) in the Rd group.1
†Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in the DARZALEX® + Rd arm were: headache, urinary tract infection, hyperglycemia, hypocalcemia, vomiting, chills, paresthesia, and hypertension.1
Serious adverse reactions with a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia (DRd 15% vs Rd 8%), bronchitis (DRd 4% vs Rd 2%), and dehydration (DRd 2% vs Rd <1%).1
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
Most frequent laboratory abnormalities reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Rd arm1
Treatment-emergent laboratory abnormalities1
Rd=lenalidomide (R) + dexamethasone (d).
- Discontinuation rates due to any adverse event: 7% with DRd vs 16% with Rd
- Infusion-related reactions (IRRs) with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
Frequency of IRRs (any grade) across clinical trials (N=2066)1
IRRs=infusion-related reactions.
Most IRRs occurred during the first infusion across clinical trials (N=2066)1
- For 37% of patients, infusion-related reactions (IRRs; any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
- Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
- Incidence of infusion modification due to reactions was 36%
- DARZALEX® can cause severe IRRs. Severe IRRs included 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 symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
- 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®
Management of IRRs
For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1
IRR=infusion-related reaction.
Interference with serological testing1
DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.
Reminders
- Type and screen patients before starting DARZALEX®
- Inform blood banks when a patient is on DARZALEX®
- Identify any DARZALEX®-treated blood samples
- Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Brochure on daratumumab and serological testing
Identification card to give to patients taking daratumumab
You are now viewing a follow-up analysis of the MAIA study. This information is not included in the current Prescribing Information and has not been evaluated by the FDA.
DARZALEX® + Rd offers your patients a frontline treatment that’s supported by 56 months of safety evaluation3*
Most frequent treatment-emergent adverse events as observed (any grade reported in ≥30% of patients and/or Grade 3/4 reported in ≥10% of patients) in the DARZALEX® + Rd arm3†
Adverse reactions and laboratory abnormalities reported in ~5-year follow-up3
Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
*Median duration of study treatment was 56.6 months (range: 53.0–60.1 months) in the DRd group and 55.9 months (range: 52.5–59.4 months) in the Rd group.3
†Safety analysis set. TEAEs are defined as any adverse event (AE) that occurs after start of the first study treatment through 30 days after the last study treatment; or the day prior to start of subsequent antimyeloma therapy, whichever is earlier; or any AE that is considered drug related (very likely, probably, or possibly related) regardless of the start date of the event; or any AE that is present at baseline but worsens in toxicity grade or is subsequently considered drug related by the investigator.
Additional TEAEs (any grade ≥20% and/or Grade 3/4 ≥10%) reported in the DARZALEX® + Rd arm were thrombocytopenia, arthralgia, nasopharyngitis, decreased appetite, upper respiratory tract infection, pyrexia, headache, pain in extremity, dizziness, and vomiting.3
Treatment-emergent adverse events are reported as observed. These analyses have not been adjusted for multiple comparisons and no conclusions should be drawn.
- Cumulative Grade 3/4 infection rates were 41% for DRd vs 29% for Rd3
- Cumulative rates of discontinuation due to TEAEs were 13% for DRd vs 22% for Rd3
- Hematologic adverse events included in the follow-up analyses are investigator-reported TEAEs and not investigator-reported treatment-emergent laboratory abnormalities
- DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d).
Frequency of IRRs (any grade) across clinical trials (N=2066)1
Less than 1% of patients had a Grade 3/4 IRR at Week 2 or subsequent infusions.
IRRs=infusion-related reactions.
Most IRRs occurred during the first infusion across clinical trials (N=2066)1
- For 37% of patients, infusion-related reactions (IRRs; any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
- Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
- Incidence of infusion modification due to reactions was 36%
- DARZALEX® can cause severe IRRs. Severe IRRs included 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 symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
- 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®
Management of IRRs
For IRRs of any grade/severity, immediately interrupt the DARZALEX® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX® as outlined below.1
IRR=infusion-related reaction.
Interference with serological testing1
DARZALEX® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX® infusion.
Reminders
- Type and screen patients before starting DARZALEX®
- Inform blood banks when a patient is on DARZALEX®
- Identify any DARZALEX®-treated blood samples
- Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Brochure on daratumumab and serological testing
Identification card to give to patients taking daratumumab
Keep patients on a proven path
For the best chance of achieving the progression-free survival or sustained responses seen in the MAIA trial, patients should be treated with frontline DRd until disease progression or unacceptable toxicity1
Please review MAIA primary analysis, including study design, efficacy, and safety
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
In a post hoc subset analysis of patients treated for at least 18 months
Treatment duration and long-term outcomes with frontline DRd4,7
You are now viewing a post hoc subset analysis by treatment duration of the MAIA trial. This information is not included in the current Prescribing Information and has not been evaluated by the US Food and Drug Administration. No conclusions should be drawn. These data should be understood in the context of the methodology.
Methodology
- 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 months4,7
- This post hoc subset analysis was based on patients who were treated for at least 18 months and excluded patients who discontinued therapy due to disease progression during the first 18 months4,7
- For the DRd arm, it 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. For the Rd arm, it included 204 patients who were treated for at least 18 months, out of 369 patients of the primary ITT analysis of the MAIA trial1,4,7
- Response data presented are cumulative deepest response rates achieved by 6, 9, and 18 months for patients who continued all study treatment for at least 18 months
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
≥CR with DRd
More patients achieved a ≥CR by 18 months vs 6 months of DRd4,7
≥CR rates increased over 6, 9, and 18 months of continuous frontline DRd.4,7
~50% of patients achieved a ≥CR by 18 months of DRd treatment compared with ~9% by 6 months of treatment4,7
CR=complete response; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ORR=overall response rate; PR=partial response; sCR=stringent complete response; VGPR=very good partial response.
≥CR with Rd alone
≥CR by 18 months vs 6 months of Rd4,7
≥CR rates increased over 6, 9, and 18 months of continuous frontline Rd.4,7
~30% of patients achieved a ≥CR by 18 months of Rd treatment compared with ~4% by 6 months of treatment4,7
CR=complete response; ORR=overall response rate; PR=partial response; Rd= lenalidomide (R) + dexamethasone (d); sCR=stringent complete response; VGPR=very good partial response.
More patients achieved a ≥CR with DRd vs Rd among patients treated for at least 18 months (49.8% vs 30.4%, respectively)4,7
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
When treated until disease progression or unacceptable toxicity
Patients achieved longer duration of response with continuous DRd vs continuous Rd1,2
You are now viewing the 28-month analysis of the MAIA study.
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d).
*Responders were defined as patients who achieved a partial response or better.2
- Median duration of response was not reached with DRd vs 34.7 months (95% CI, 30.8-not estimable) for Rd alone1†
†Median follow-up was 28 months (range: 0.0-41.4 months).2
You are now viewing a follow-up analysis of the MAIA study. This information is not included in the current Prescribing Information and has not been evaluated by the US Food and Drug Administration.
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); IQR=interquartile range; Rd=lenalidomide (R) + dexamethasone (d).
*Responders were defined as patients who achieved a partial response or better.4
- Patients achieved longer duration of response with continuous DRd (a triplet regimen) vs continuous Rd (a doublet regimen)3,4
These analyses were not statistically adjusted for multiple comparisons. No conclusions should be drawn.
†Median follow-up was 56 months in the DRd group (IQR: 53.0-60.1) and in the Rd group (IQR: 52.5-59.4).1,3
In patients who continued treatment:
An evaluation of frequently reported TEAEs over time from treatment initiation to ~30 months4
You are now viewing a subset analysis by treatment duration of the MAIA trial. This information is not included in the current Prescribing Information and has not been evaluated by the FDA. 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.
Methodology
- Most frequently reported treatment-emergent adverse events (TEAEs) that met the threshold of cumulative any grade TEAE >30% or Grade 3/4 TEAE >10% are presented4
- Combined TEAE rates are the sum of the percentages of the most frequently reported TEAEs, at each cycle period
- Percentages represent number of patients with >1 TEAE by treatment cycle divided by total number of patients treated within the treatment window
- Only TEAEs with 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
- Decrease in adverse event (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 (see rates below)4
- 13% of intent-to-treat (ITT) patients discontinued treatment due to a TEAE with DRd (n=364) vs 22% with Rd alone (n=365)3
TEAEs: DRd
In patients who continued treatment:
Most AE rates decreased over time from treatment initiation to ~30 months for DRd4
AEs for DRd across Cycles 1-304
Any TEAE ≥30% or Grade 3/4 ≥10%
Scroll to view data over time
| DARZALEX® once-monthly administration start | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Any Grade TEAE |
Cycles 1-2 (n=364) |
Cycles 3-6 (n=348) |
Cycles 7-10 (n=330) |
Cycles 11-14 (n=312) |
Cycles 15-18 (n=299) |
Cycles 19-22 (n=285) |
Cycles 23-26 (n=271) |
Cycles 27-30 (n=259) |
|
| Hematologic | Neutropenia | 40.4% | 24.4% | 17.9% | 18.6% | 17.7% | 16.1% | 11.1% | 12.4% |
| Anemia | 17.3% | 10.9% | 8.2% | 6.7% | 4.0% | 6.0% | 5.5% | 7.3% | |
| Leukopenia | 14.0% | 5.7% | 4.2% | 3.8% | 3.0% | 3.5% | 4.1% | 2.3% | |
| Lymphopenia | 13.7% | 4.6% | 3.6% | 4.8% | 5.7% | 4.2% | 4.4% | 3.5% | |
| Nonhematologic | Constipation | 26.4% | 11.8% | 5.5% | 3.8% | 4.0% | 2.1% | 3.0% | 5.0% |
| Nausea | 21.4% | 6.6% | 4.2% | 3.8% | 5.0% | 1.8% | 2.6% | 1.9% | |
| Fatigue | 20.1% | 14.1% | 7.0% | 8.7% | 7.4% | 7.7% | 5.9% | 7.3% | |
| Diarrhea | 15.9% | 15.5% | 15.8% | 16.0% | 18.4% | 17.5% | 14.0% | 10.0% | |
| Dyspnea | 14.8% | 6.6% | 3.9% | 3.2% | 1.7% | 3.2% | 2.2% | 2.3% | |
| Edema peripheral | 14.3% | 12.6% | 7.3% | 7.7% | 6.4% | 6.3% | 4.1% | 4.2% | |
| Cough | 14.0% | 6.9% | 3.9% | 2.9% | 3.0% | 4.2% | 4.8% | 3.1% | |
| Asthenia | 13.5% | 8.9% | 7.3% | 6.7% | 6.0% | 6.0% | 3.7% | 2.7% | |
| Muscle spasms | 13.5% | 9.5% | 2.1% | 5.4% | 2.3% | 2.5% | 2.6% | 1.2% | |
| Back pain | 9.9% | 6.3% | 6.4% | 5.1% | 4.0% | 6.7% | 3.7% | 5.4% | |
| Insomnia | 9.9% | 7.2% | 5.2% | 7.4% | 3.0% | 4.2% | 3.0% | 3.1% | |
| Weight decreased | 9.1% | 12.4% | 4.5% | 3.8% | 1.3% | 2.5% | 1.1% | 1.9% | |
| Hypokalemia | 8.0% | 4.6% | 3.3% | 1.6% | 3.0% | 6.0% | 2.2% | 4.2% | |
| Peripheral neuropathy | 6.3% | 4.0% | 5.2% | 5.4% | 5.4% | 7.0% | 2.6% | 3.1% | |
| Bronchitis | 4.7% | 6.6% | 6.4% | 7.1% | 8.7% | 6.7% | 6.6% | 7.3% | |
| Pneumonia | 4.7% | 6.6% | 3.9% | 4.2% | 4.7% | 5.3% | 3.3% | 2.3% | |
| Cataract | 0.3% | 0.6% | 2.4% | 3.5% | 5.4% | 3.9% | 3.7% | 4.6% | |
|
Combined TEAE rates (sum of the percentages) |
292% | 186% | 128% | 130% | 120% | 123% | 94% | 95% | |
AE=adverse event; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
Cycle=28 days.
In patients who continued treatment:
Combined rates of frequently reported TEAEs decreased over time from treatment initiation to ~30 months for DRd4
AE=adverse event; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
TEAEs: Rd alone
In patients who continued treatment:
AE rates over time from treatment initiation to ~30 months for Rd4
AEs for Rd across Cycles 1-304
Any TEAE ≥30% or Grade 3/4 ≥10%
Scroll to view data over time
| Any Grade TEAE |
Cycles 1-2 (n=365) |
Cycles 3-6 (n=335) |
Cycles 7-10 (n=297) |
Cycles 11-14 (n=263) |
Cycles 15-18 (n=237) |
Cycles 19-22 (n=210) |
Cycles 23-26 (n=187) |
Cycles 27-30 (n=169) |
|
|---|---|---|---|---|---|---|---|---|---|
| Hematologic | Neutropenia | 20.3% | 21.8% | 12.8% | 16.0% | 14.8% | 9.0% | 13.4% | 13.0% |
| Anemia | 19.5% | 16.1% | 8.1% | 8.0% | 10.1% | 5.7% | 3.7% | 5.3% | |
| Leukopenia | 4.4% | 2.4% | 1.3% | 3.0% | 3.0% | 2.4% | 2.7% | 4.1% | |
| Lymphopenia | 7.1% | 5.7% | 2.0% | 3.4% | 1.7% | 1.9% | 0.5% | 3.0% | |
| Nonhematologic | Constipation | 19.7% | 14.0% | 4.0% | 3.4% | 4.2% | 2.4% | 3.7% | 1.8% |
| Nausea | 15.6% | 6.0% | 4.0% | 2.3% | 2.1% | 3.8% | 2.1% | 0.0% | |
| Fatigue | 16.2% | 8.4% | 6.1% | 5.7% | 5.5% | 4.3% | 2.7% | 5.9% | |
| Diarrhea | 15.6% | 15.2% | 12.5% | 12.5% | 15.6% | 14.8% | 9.1% | 12.4% | |
| Dyspnea | 6.6% | 3.0% | 3.4% | 3.0% | 2.5% | 2.9% | 1.6% | 1.2% | |
| Edema peripheral | 11.8% | 12.5% | 6.4% | 3.8% | 5.5% | 6.7% | 4.8% | 4.7% | |
| Cough | 5.8% | 3.3% | 3.7% | 2.3% | 5.1% | 1.0% | 2.1% | 2.4% | |
| Asthenia | 9.6% | 5.7% | 6.4% | 4.2% | 5.1% | 3.3% | 2.7% | 5.9% | |
| Muscle spasms | 10.7% | 6.9% | 5.4% | 3.8% | 2.5% | 3.8% | 2.7% | 1.2% | |
| Back pain | 6.8% | 8.1% | 5.7% | 6.5% | 4.6% | 7.1% | 5.9% | 3.6% | |
| Insomnia | 12.6% | 9.3% | 6.7% | 5.7% | 5.1% | 2.9% | 2.1% | 4.1% | |
| Weight decreased | 7.1% | 6.6% | 2.7% | 1.5% | 4.2% | 2.9% | 1.6% | 1.2% | |
| Hypokalemia | 4.9% | 5.4% | 4.0% | 4.6% | 4.6% | 5.2% | 3.7% | 1.8% | |
| Peripheral neuropathy | 3.8% | 3.6% | 3.7% | 4.9% | 3.8% | 4.3% | 0.5% | 4.1% | |
| Bronchitis | 3.0% | 5.4% | 5.4% | 4.9% | 6.8% | 7.1% | 5.9% | 6.5% | |
| Pneumonia | 3.3% | 4.5% | 3.7% | 2.7% | 2.1% | 1.0% | 1.6% | 3.6% | |
| Cataract | 0.8% | 1.5% | 1.7% | 5.3% | 4.6% | 6.7% | 7.5% | 4.1% | |
|
Combined TEAE rates (sum of the percentages) |
205% | 165% | 110% | 108% | 114% | 99% | 81% | 90% | |
AE=adverse event; Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
Cycle=28 days.
TEAEs: Combined
In patients who continued treatment:
Combined rates of frequently reported TEAEs decreased over time from treatment initiation to ~30 months for DRd and Rd4
AE=adverse event; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
Keep your patients engaged throughout treatment by establishing clear treatment and personal goals
Help your patients understand the long-term safety profile and proven efficacy of continuous treatment with DRd with the EMMY approach
EXPECTATIONS
Set clear expectations at the start of treatment—and beyond—to prepare patients and caregivers for their journey ahead
MOTIVATION
Motivate patients through continued education to help them stay on track with DRd and reach their treatment goals
MILESTONES
Recognize milestones, including responses and dosing frequency, to encourage compliance with treatment
YOUR CARE TEAM
Establish strong collaboration between you, the care team, and the patient to provide guidance and resources for the duration of therapy
Clinical results of frontline DARZALEX® + Rd treatment for high-risk patients
These analyses are not included in the Prescribing Information for DARZALEX®. These analyses were not adjusted for multiple comparisons. There are insufficient numbers of patients per subgroup to make definitive conclusions of efficacy among the subgroups.
More high-risk patients continued living without progression with frontline DARZALEX® + Rd vs Rd alone2,3
DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); mPFS=median progression-free survival; Rd=lenalidomide (R) +
dexamethasone (d).
PFS numerically favored frontline DARZALEX® + Rd in most subgroups vs Rd alone after 28 months of follow-up2*
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG= Eastern Cooperative Oncology Group; IgG=immunoglobulin G; ISS=International Staging System; NE=not estimable; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
*Median follow-up was 28 months (range: 0.0-41.4 months).2
†Per protocol, cytogenetic tests from bone marrow aspirates were performed by local laboratories at screening, and 642 patients had baseline cytogenetic data reported from local laboratories out of the 737 patients who were enrolled in MAIA.4,5
‡Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotype analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality (del17p, t[14;16], or t[4;14]).2
PFS continued to numerically favor patients on frontline DARZALEX® + Rd vs Rd alone after 56 months of follow-up3*
CI=confidence interval; CrCl=creatinine clearance; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG=Eastern Cooperative Oncology Group; IgG=immunoglobulin G; IQR=interquartile range; ISS=International Staging System; NE=not estimable; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
*Median follow-up was 56 months in the DRd group (IQR: 53.0-60.1) and in the Rd group (IQR: 52.5-59.4).1,3
†Per protocol, cytogenetic tests from bone marrow aspirates were performed by local laboratories at screening, and 642 patients had baseline cytogenetic data reported from local laboratories out of the 737 patients who were enrolled in MAIA.4,5
‡Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotype analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality (del17p, t[14;16], or t[4;14]).2
DRd treatment in frail patient subgroup
Clinical results of frontline DARZALEX® + Rd treatment for frail patients
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.
Post hoc subgroup analysis of MAIA by frailty status score8
Frailty assessment was performed retrospectively using age, CCI, and baseline ECOG PS score8
CCI=Charlson Comorbidity Index; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group Performance Status; Rd=lenalidomide (R) + dexamethasone (d).
The median age in frail subgroup was 77 years (range: 57-90 years), with 88% of patients having ECOG performance score ≥1. CCI was calculated based on retrospective review of each patient's medical history.8
Limitations: The retrospective assessment of frailty score was a limitation of this study. Retrospective CCI 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. The ECOG PS score parameter used for frailty score calculations in the study is more subjective, with susceptibility to intra- and inter-observer bias, compared with the ADL and IADL scales used in the IMWG scoring system. 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 assessments that more accurately reflect biological or functional frailty will remain important for the further optimization of treatment strategies for frail patients. Patients with an ECOG PS score ≥3 and patients with comorbidities that may interfere with the study procedures were excluded from MAIA; the inclusion and exclusion criteria for the study limits the generalizability of these results to more frail patients seen in clinical practice.8
ADL=activities of daily living; IADL=instrumental activities of daily living.
More frail patients continued living without progression with frontline DARZALEX® + Rd vs Rd alone8
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; mPFS=median progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
In a subgroup analysis of frail patients after 36.4 months of follow-up, 61.5% of patients had not progressed with DARZALEX® + Rd vs 39.5% of patients with Rd alone8
CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).
Most frequent Grade 3/4 TEAEs (≥10%) in frail patients8
AE=adverse event; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.
Additional safety information: results from Prescribing Information1,9
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 than in younger patients. Among patients with relapsed and refractory multiple myeloma (n=1213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.
Of the 214 patients who received DARZALEX FASPRO® as combination therapy with pomalidomide and dexamethasone or DARZALEX FASPRO® as combination therapy with lenalidomide and low-dose dexamethasone for relapsed and refractory multiple myeloma, 43% were 65 to <75 years of age, and 18% were 75 years of age or older.
Adverse reactions occurring at a higher frequency (≥5% difference) in patients ≥65 years of age included fatigue, pyrexia, peripheral edema, urinary tract infection, diarrhea, constipation, vomiting, dyspnea, cough, and hyperglycemia. Serious adverse reactions occurring at a higher frequency (≥2% difference) in patients ≥65 years of age included neutropenia, thrombocytopenia, diarrhea, anemia, COVID-19, ischemic colitis, deep vein thrombosis, general physical health deterioration, pulmonary embolism, and urinary tract infection.
No clinically meaningful differences in the pharmacokinetics of daratumumab were observed in geriatric patients compared to younger adult patients.
DRd treatment in high-risk patient subgroup