Despite significant advancements in therapy of multiple myeloma (MM) over the past 20 years, most patients experience relapse, necessitating new treatment approaches. This study aims to compare the real-world effectiveness of lenalidomide (LEN)-based triplet therapies, specifically daratumumab (DRD), carfilzomib (KRD), and ixazomib (IRD), in relapsed/refractory multiple myeloma (RRMM).

A retrospective registry-based study analyzed 538 RRMM patients undergoing therapy for their first to third relapse. The primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), with a matching-adjusted indirect comparisons (MAIC) employed to address cohort differences.

ORR was highest for DRD at 91.4%, followed by KRD (89.6%) and IRD cohorts (Early-IRD: 79.6%, Late-IRD: 70.8%). Median PFS for DRD was greater at 23.64 months compared to KRD (16.52 months) and IRD groups (Early-IRD: 19.97 months, Late-IRD: 11.57 months). The MAIC confirmed better outcomes for the DRD regimen. High-risk features were not overcome by any of the LEN-based regimens.

The findings underscore the superior efficacy of DRD in achieving sustained responses in RRMM patients. The composition of the cohort is a crucial factor, extending beyond selection criteria. This study highlights the importance of real-world evidence in assessing treatment modalities in clinical settings.