MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant
Adding the CD38 antibody daratumumab to standard lenalidomide-dexamethasone cut the risk of progression or death by about 44% in older myeloma patients, and later extended survival.
MAIA randomised 737 transplant-ineligible patients with newly diagnosed multiple myeloma (median age 73) to daratumumab plus lenalidomide and dexamethasone (D-Rd) or Rd alone, both continued until progression. The primary endpoint was PFS. At 30 months PFS was 70.6% versus 55.6% (hazard ratio 0.56); complete response or better was 47.6% versus 24.9% and MRD-negativity 24.2% versus 7.3%. Longer follow-up showed a significant overall survival benefit (hazard ratio about 0.68; five-year OS roughly 66% versus 53%). Neutropenia and pneumonia were more frequent with daratumumab.
- 737 transplant-ineligible patients; D-Rd vs Rd until progression.
- 30-month PFS 70.6% vs 55.6%; hazard ratio 0.56.
- Complete response or better 47.6% vs 24.9%; MRD-negativity (10^-5) 24.2% vs 7.3%.
- Overall survival significantly improved at longer follow-up (HR about 0.68; 5-year OS roughly 66% vs 53%).
- Grade 3-4 neutropenia 50.0% vs 35.3%; pneumonia 13.7% vs 7.9%.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
- Continuous therapy until progression; treatment burden and cost are substantial.
- Patients over 80 and very frail patients were under-represented.
- Median PFS was not reached at the primary analysis; the durability estimate relies on later reports.
- Comparator Rd is itself now being displaced by quadruplets.