Daratumumab in the frontline management of newly diagnosed multiple myeloma: An overview of systematic reviews and meta-analyses.
Riddhi Solanki, Manju Sengar, Hasmukh Jain248
Background:
We conducted an overview of systematic reviews and meta-analyses (SRMAs) to evaluate daratumumab’s effect on overall survival (OS) in frontline newly diagnosed multiple myeloma (NDMM), as OS benefit remains uncertain despite improved progression-free survival.
Methods:
Registered in PROSPERO (CRD420261298985), we searched 4 databases from inception to January 31, 2026 for SRMAs evaluating daratumumab-based induction regimens reporting OS estimates. Method quality assessed using AMSTAR-2 and certainty of evidence using GRADE.
Results:
8 SRMAs (2019–2025) were included, synthesizing a mean of 8.2 daratumumab-specific RCTs per review. Across regimens, daratumumab-containing therapy consistently reduced mortality vs. standard regimens, with varied certainty. The most robust OS benefit was observed with D-VTd (CASSIOPEIA: HR 0.55, 95% CI 0.42–0.73; high certainty) and D-Rd (MAIA: HR 0.67, 95% CI 0.55–0.82; high certainty). D-VMp also showed survival improvement (ALCYONE: HR 0.56, 95% CI 0.46–0.68; moderate certainty). For D-VRd, OS favored daratumumab but was imprecise (GRIFFIN: HR 0.90, 95% CI 0.31–2.56; moderate certainty). Evidence for D-VCd was limited (HR 1.33, 95% CI 0.69–2.55; low), and no mature OS data for D-KRd (very low certainty). Overall OS evidence was rated moderate, primarily downgraded for imprecision.
Conclusions:
Adding daratumumab improves OS in NDMM, supported by moderate-to-high certainty evidence with the most mature benefit seen for D-VTd, D-Rd, and D-VRd, supporting routine use; however, comparator arms are often inferior (quadruplets vs triplets vs doublets), limiting incremental inference. Longer follow-up is needed to clarify optimal sequencing.
OS outcomes associated with frontline daratumumab-based regimens in newly diagnosed multiple myeloma (NDMM). Hazard ratios (HRs) <1.0 favor daratumumab-containing therapy over standard-of-care comparator regimens.