MAIA frailty subgroup analysis: long-term follow-up with daratumumab plus lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma.

In MAIA (Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus Rd in transplant-ineligible newly diagnosed multiple myeloma (NDMM). Here, we report an updated subgroup analysis by frailty status. We retrospectively performed frailty assessments using age, Charlson Comorbidity Index, and baseline Eastern Cooperative Oncology Group performance status score; patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. After a 64.5-month median follow-up, OS benefit of D-Rd versus Rd was maintained in the non-frail subgroup (median, not reached [NR] vs 69.8 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37-0.76; P = 0.0004); the OS HR point estimate favored D-Rd versus Rd in the frail subgroup (NR vs 50.4 months; HR, 0.79; 95% CI, 0.58-1.06; P = 0.1128). Improved PFS and rates of complete response or better and minimal residual disease negativity (10-5) were observed with D-Rd versus Rd across frailty subgroups. Duration of therapy was consistently longer with D-Rd versus Rd, highlighting the improved disease control and long-term tolerability of daratumumab in frail patients. These long-term data, although limited by the retrospective assessment of frailty using baseline characteristics, continue to support the therapeutic benefit of D-Rd in terms of improved PFS and higher rates of deep responses in transplant-ineligible NDMM, regardless of frailty status.