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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 ~30 months and ~5 years

A large, randomized, open-label, multicenter, active-controlled phase 3 trial1

3.1_maia-study-design_desktop

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

maia_table_study_design_demographics

ECOG=Eastern Cooperative Oncology Group; ISS=International Staging System; Rd=lenalidomide (R) + dexamethasone (d).

*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

See subgroup analyses

National Comprehensive Cancer Network® (NCCN®) Category 1, preferred

Daratumumab* 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 V5.2022.
© National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed March 9, 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 ~30 months of treatment1*

3.1_maia-pfs-30-months_desktop

CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; 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 ~30 months of follow-up:
Deep responses for a strong start. Durable responses to keep your patients' treatment journeys moving forward1*

maia-orr-30-months

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 at median follow-up of ~30 months.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 ~30 months of follow-up:
Patients experienced MRD negativity with DARZALEX® + Rd at a rate 3x greater than Rd alone1*†

3.4x greater MRD negativity with DRd1

3.1_maia-mrd_desktop

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 at median follow-up of ~30 months.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

At ~5 years, frontline DARZALEX® + Rd significantly reduced the risk of death vs Rd alone1,3*

Maia Os 5 Year Chart Desktop

CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; OS=overall survival; Rd=lenalidomide (R) + dexamethasone (d).

*Median follow-up was 56 months in the DRd group (range: 53.0-60.1 months) and in the Rd group (range: 52.5-59.4 months).1,3

†Kaplan-Meier estimate.3

At ~5 years: 66% of patients were still alive with DARZALEX® + Rd vs 53% with Rd alone (DRd, 95% CI: 61, 71; Rd, 95% CI: 47, 59)1,3

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.

After ~5 years of follow-up:
More patients continued living without progression with frontline DARZALEX® + Rd3*

Maia PFS 5 Years desktop

CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).

*Median follow-up was 56 months in the DRd group (range: 53.0-60.1 months) and in the Rd group (range: 52.5-59.4 months).3

†Kaplan-Meier estimate.3

At ~5 years: 52.5% of patients had not progressed with DRd vs 28.7% of patients in the Rd group (DRd, 95% CI: 46.7, 58.0; Rd, 95% CI: 23.1, 34.6)3

The follow-up analysis was not adjusted for multiplicity and conclusions should not be drawn.

Cumulative response rates after ~5 years of follow-up

Cumulative ORRs3

3.1_maia-orr-5-years_desktop

CR=complete response; ORR=overall response rate; PR=partial response; Rd=lenalidomide (R) + dexamethasone (d); sCR=stringent complete response; VGPR=very good partial response.

†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 at median follow-up of 47.9 months.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 patients

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

Maia Tornado Chart Safety Desktop

Rd=lenalidomide (R) + dexamethasone (d).

*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

Maia Tornado chart 2 Desktop

Rd=lenalidomide (R) + dexamethasone (d).

Frequency of IRRs (any grade) across clinical trials (N=2066)1

Clinical trials irrs frequency

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

Management of irrs

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

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

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 ~5 years of safety evaluation*

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

Maia Tornado 5 year chart

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.

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.

  • 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

DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d).

Frequency of IRRs (any grade) across clinical trials (N=2066)1

Clinical trials irrs frequency

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

Management of irrs

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

Download brochure

Identification card to give to patients taking daratumumab

Download ID card

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

3.1_maia_subgroup_high_risk_patients_desktop-1

DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); mPFS=median progression-free survival; Rd=lenalidomide (R) +
dexamethasone (d).

In the 3-year subgroup analysis, PFS numerically favored DARZALEX® + Rd in most subgroups vs Rd alone2

maia_high_risk_subpop_3yr

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).

*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 in the ~5-year subgroup follow-up3

maia_high_risk_subpop_5yr

CI=confidence interval; CrCl=creatinine clearance; 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).

*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

View results

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 score4

Frailty assessment was performed retrospectively using age, CCI, and baseline ECOG PS score4

3.1_maia-frailty-study-design_desktop

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.4

Authors' 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 (activities of daily living) and IADL (instrumental activities of daily living) 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.4

ADL=activities of daily living; IADL=instrumental activities of daily living.

More frail patients continued living without progression with frontline DARZALEX® + Rd vs Rd alone4

Maia 3yr subgroup frailty

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 3-year subgroup analysis of frail patients, 61.5% of patients had not progressed with DARZALEX® + Rd vs 39.5% of patients with Rd alone4

maia-frail-patient-pfs

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 patients4

Maia frailty safety

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 Information1,5

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

View results

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