Background
Final survival analysis of the phase 3 randomized MAIA trial of daratumumab plus lenalidomide/dexamethasone (D-Rd) versus lenalidomide/dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma (NDMM). 737 patients were randomized (D-Rd 368; Rd 369). A 2021 protocol amendment enabled a long-term extension for overall survival follow-up.
Results
Interventions and follow up: Arm A: daratumumab + lenalidomide + dexamethasone (D-Rd) until progression
Arm B: lenalidomide + dexamethasone (Rd) until progression
Primary endpoint: progression-free survival (prior analyses); this report presents long-term overall survival (OS)
mFollow up: 89.3 months
Results: OS: median 90.3 (95% CI 80.8–NE) vs 64.1 (56.0–70.8) months, HR 0.67 (95% CI 0.55–0.82); 7-year OS 53.1% vs 39.3%
Time to next therapy: not reached vs 42.4 months, HR 0.51 (95% CI 0.41–0.63), P<.0001
Arm B: lenalidomide + dexamethasone (Rd) until progression
Primary endpoint: progression-free survival (prior analyses); this report presents long-term overall survival (OS)
mFollow up: 89.3 months
Results: OS: median 90.3 (95% CI 80.8–NE) vs 64.1 (56.0–70.8) months, HR 0.67 (95% CI 0.55–0.82); 7-year OS 53.1% vs 39.3%
Time to next therapy: not reached vs 42.4 months, HR 0.51 (95% CI 0.41–0.63), P<.0001
Adverse events
Death due to AE: 12% (D-Rd, 44/364) vs 11% (Rd, 40/365)
Conclusions
With more than 7 years of follow-up, D-Rd established a new median OS benchmark of 7.5 years in transplant-ineligible NDMM, a >26-month absolute median OS gain over Rd. These mature data reinforce frontline daratumumab-based triplet therapy to maximize survival in this population.
Key Limitations
The Rd comparator, appropriate at enrollment, is now dated as anti-CD38 quadruplets emerge; the trial was open-label; the long-term extension permitted subsequent anti-myeloma therapies (including daratumumab) in the control arm, which may attenuate the observed OS difference; there is no head-to-head comparison with newer quadruplet regimens.
Clinical Context
D-Rd is FDA-approved (2019) and an NCCN category 1 preferred regimen for transplant-ineligible NDMM. Emerging quadruplet/anti-CD38 regimens (e.g., D-VRd in CEPHEUS, isatuximab-VRd in IMROZ/BENEFIT) are now competing frontline standards; MAIA final OS remains a key benchmark for the triplet backbone.