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APPROVED

DARZALEX FASPRO® + VRd is approved in transplant-ineligible patients with newly diagnosed multiple myelomaNDMM1

DARZALEX FASPRO® monotherapy is the first and only FDA-approved treatment in high-risk smoldering multiple myeloma1DARZALEX FASPRO® monotherapy is now approved in high-risk smoldering multiple myeloma1

Age Subgroup
(Post Hoc Analysis)

The age-specific subgroup analyses were conducted post hoc, are not included in the Prescribing Information for DARZALEX®, and have not been evaluated by the FDA; no conclusions should be drawn.

Please see MAIA trial design & primary results

Methodology

MAIA: A clinical study of DARZALEX® + Rd vs Rd alone in newly diagnosed, transplant-ineligible patients with multiple myeloma1

Post hoc subgroup analysis of patients from the MAIA study based on age

Approval of DARZALEX® for transplant-ineligible adult patients with newly diagnosed multiple myeloma was based on a large, randomized, open-label, multicenter, active-controlled phase 3 trial1-3

Baseline demographics and disease characteristics were similar between the 2 treatment groups1

MAIA study primary endpoint:

Progression-free survival (PFS) based on International Myeloma Working Group (IMWG) criteria1,2

MAIA study key secondary endpoints included:

Percentage of patients with complete response (CR), 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 safety1,2

MAIA study post hoc analysis based on age:

The MAIA trial reported updated safety and efficacy data from age subgroups (<70, ≥70 to <75, ≥75, and ≥80 years) with a median follow-up of 64.5 months (range, 0-77.6).3

After 64.5 months of follow-up:

Post hoc analysis of MAIA evaluating long-term outcomes in age subgroups3*

View the efficacy results for patients aged ≥80 years including PFS, OS, MRD-negativity rates, and response rates

del=deletion; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group performance status; FDA=U.S. Food and Drug Administration; IgA=immunoglobulin A; IgD=immunoglobulin D; IgE=immunoglobulin E; IgG=immunoglobulin G; IgM=immunoglobulin M; ISS=International Staging System; ITT=intent-to-treat; Rd=lenalidomide (R) + dexamethasone (d); t=translocation.

*Median follow-up was 64.5 months.3

†ECOG performance status is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.4

‡ISS disease stage was based on the combination of serum β2-microglobulin and albumin.4

§Includes IgD, IgM, IgE, and biclonal.4

||Cytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).4

Post hoc analysis for DRd and Rd, tablePost hoc analysis for DRd and Rd, table

Patient demographics4

View the efficacy results for patients aged ≥80 years including PFS, OS, MRD-negativity rates, and response rates

del=deletion; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group performance status; FDA=U.S. Food and Drug Administration; IgA=immunoglobulin A; IgD=immunoglobulin D; IgE=immunoglobulin E; IgG=immunoglobulin G; IgM=immunoglobulin M; ISS=International Staging System; ITT=intent-to-treat; Rd=lenalidomide (R) + dexamethasone (d); t=translocation.

*Median follow-up was 64.5 months.3

†ECOG performance status is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.4

‡ISS disease stage was based on the combination of serum β2-microglobulin and albumin.4

§Includes IgD, IgM, IgE, and biclonal.4

||Cytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).4

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.

Efficacy (≥80 Years)

Progression-free survival in very elderly (≥80 years of age) patients3

mPFS 52.2 months for DRd vs 30.4 months for Rd (HR=0.48; 95% CI: 0.31-0.76)3

Observed overall survival in very elderly (≥80 years of age) patients3

MRD-negativity rates for DARZALEX® + Rd vs Rd alone in very elderly
(≥80 years of age) patients3

Response rates in patients ≥80 years of age3

ORRs, rates of ≥CR, and rates of ≥VGPR were higher for DARZALEX® + Rd vs Rd alone across all age subgroups. In those ≥80 years:

  • The ORR in the DRd group was 89.4% vs 77.5% in the Rd alone group
  • The ≥CR rate in the DRd group was 43.9% vs 21.1% in the Rd alone group
  • The ≥VGPR rate in the DRd group was 75.8% vs 43.7% in the Rd alone group

CI=confidence interval; CR=complete response; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; mPFS=median progression-free survival; MRD=minimal residual disease; ORR=overall response rate; Rd=lenalidomide (R) + dexamethasone (d); VGPR=very good partial response.

Efficacy
(<70, ≥70 to <75, ≥75 Years)

In a post hoc subgroup analysis of patients under 70 years of age:

Median PFS was not reached with frontline DARZALEX® + Rd vs 39.2 months with Rd alone3,5*

Progression-free survival (PFS)3,5

Progression-free survival: < 70 years, graphProgression-free survival: < 70 years, graph

At 60 months, 67% of patients had not progressed with DRd vs 29% with Rd alone5†

This analysis was conducted post hoc and no conclusions should be drawn.

View PFS for ages ≥70 to <75 years

 CI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NR=not reached; PFS=progression-free survival; Rd=lenalidomide (R) + dexamethasone (d).

*Median follow-up was 64.5 months.3
†Kaplan-Meier estimate.5

In a post hoc subgroup analysis of patients ≥70 to <75 years of age:

Median PFS was 61.9 months with frontline DARZALEX® + Rd vs 37.5 months with Rd alone3*

Progression-free survival (PFS)3

Surviving without progression, graphSurviving without progression, graph

This analysis is not included in the Prescribing Information for DARZALEX®. This analysis was conducted post hoc, and there are insufficient numbers of patients per subgroup to make definitive conclusions for efficacy or safety among the subgroups.

View PFS for ages ≥75 years

 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 64.5 months.3

In a post hoc subgroup analysis of patients 75 years of age or older:

Median PFS was 54.3 months with frontline DARZALEX® + Rd vs 31.4 months with Rd alone3*

Progression-free survival (PFS)3

Progression-free survival: < 75 years, graphProgression-free survival: < 75 years, graph

This analysis is not included in the Prescribing Information for DARZALEX®. This analysis was conducted post hoc, and there are insufficient numbers of patients per subgroup to make definitive conclusions for efficacy or safety among the subgroups.

 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 64.5 months.3

Safety

The age-specific subgroup analyses were conducted post hoc, are not included in the Prescribing Information for DARZALEX®, and have not been evaluated by the FDA; no conclusions should be drawn.

Rates of common Grade 3/4 TEAEs in patients ≥75 years and ≥80 years were generally similar to those of the overall study population3

Grade 3/4 TEAEs occurred in 95.5% of patients in the DRd arm vs 95.0% in the Rd arm who were ≥75 years of age and 92.3% and 95.7%, respectively, in those ≥80 years of age

The most common (≥20%) Grade 3/4 TEAEs with DRd vs Rd were:

  • Neutropenia (54.1% vs 37.0%, respectively)
  • Anemia (17.0% vs 21.6%, respectively)

Grade 3/4 infection rates were 42.6% for DRd and 29.6% with Rd

Safety profile in patients ≥80 years of age

Serious TEAEs occurred in 81.5% of patients ≥80 years of age in the DRd arm and 82.9% in the Rd arm, with pneumonia being the most common (24.6% and 8.6%, respectively)

TEAEs that led to treatment discontinuation occurred in 6.2% of patients ≥80 years of age in the DRd arm and 20.0% in the Rd arm

TEAEs with an outcome of death occurred in 12.3% of patients ≥80 years of age in the DRd arm and 11.4% in the Rd arm

Of the 2,459 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. Among patients with relapsed and refractory multiple myeloma (n=1,213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis.1

Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.1

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. No overall differences in effectiveness were observed between patients ≥65 years (n=131) and <65 years (n=85).6

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.6

No clinically meaningful differences in the pharmacokinetics of daratumumab were observed in geriatric patients compared to younger adult patients.6

DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); FDA=U.S. Food and Drug Administration; Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.

Safety in patients aged ≥75 years

In an analysis of safety among patients aged ≥75 years, Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 95.5% of patients on DRd and 95.0% of patients on Rd.3

The most common (≥10%) Grade 3 or 4 TEAEs were neutropenia (DRd, 62.4%; Rd, 41.5%), lymphopenia (DRd, 21.0%; Rd, 12.6%), anemia (DRd, 20.4%; Rd, 25.2%), and pneumonia (DRd, 20.4%; Rd, 14.5%).7 Serious TEAEs occurred in 80.9% of patients on DRd and 79.2% of patients on Rd, the most common of which was pneumonia (19.7% and 12.6%, respectively).3

TEAEs with an outcome of death occurred in 11.5% of patients on DRd and 13.2% of patients on Rd alone.3

All TEAEs are reported as observed. These analyses were conducted post hoc and no conclusions should be drawn.

TEAEs led to study treatment discontinuation in 15.3% of patients on DRd and 27.7% of patients on Rd alone.3

Of the 2,459 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. Among patients with relapsed and refractory multiple myeloma (n=1,213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis.1

Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.1

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. No overall differences in effectiveness were observed between patients ≥65 years (n=131) and <65 years (n=85).6

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.6

No clinically meaningful differences in the pharmacokinetics of daratumumab were observed in geriatric patients compared to younger adult patients.6

DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d); TEAE=treatment-emergent adverse event.

References:

  1. DARZALEX® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. Facon T, Kumar S, Plesner T, et al; the MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115.
  3. Facon T, Moreau P, Weisel K, et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39:942-950.
  4. Facon T, Moreau P, Weisel K, et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950 [supplementary appendix].
  5. Facon T, Kumar SK, Weisel K, et al. Daratumumab plus lenalidomide and dexamethasone in patients with transplant-ineligible newly diagnosed multiple myeloma: MAIA age subgroup analysis. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.
  6. DARZALEX FASPRO® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  7. Moreau P, Facon T, Usmani SZ, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): clinical assessment of key subgroups of the phase 3 MAIA study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.