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.

• Keywords
• Lenalidomide triplets, Multiple myeloma, Relapsed/refractory, Risk groups,
• MeSH
• Drug Resistance, Neoplasm MeSH
• Adult MeSH
• Glycine analogs & derivatives   administration & dosage   MeSH
• Lenalidomide * administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * drug therapy   MeSH
• Multiple Myeloma * drug therapy   mortality   pathology   MeSH
• Antibodies, Monoclonal administration & dosage   therapeutic use   MeSH
• Oligopeptides administration & dosage   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Boron Compounds administration & dosage   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• carfilzomib MeSH Browser
• daratumumab MeSH Browser
• Glycine MeSH
• ixazomib MeSH Browser
• Lenalidomide * MeSH
• Antibodies, Monoclonal MeSH
• Oligopeptides MeSH
• Boron Compounds MeSH