Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis

: Lenalidomide and dexamethasone (Rd)-based triplets, in particular Carfilzomib-Rd (KRd) and Daratumumab-Rd (DaraRd), represent a standard of care in lenalidomide sensitive multiple myeloma (MM) patients in first relapse. Meta-analysis of randomized clinical trials (RCT), suggested better outcome with DaraRd. Trying to address this issue in clinical practice, we collected data of 430 consecutive MM patients addressed to Rd-based triplets in first relapse between January 2017 and March 2021. Overall, the most common used regimen was DaraRd, chosen in almost half of the cases (54.4%), followed by KRd (34.6%). Different triplets were used much less commonly. In the attempt to limit the imbalance of a retrospective analysis, we conducted a propensity score matching (PSM) comparison between DaraRd and KRd. After PSM, efficacy of DaraRd vs KRd was similar in terms of overall response rate (ORR) (OR: 0.9, p=0.685) as well as of very good partial response (VGPR) or better (OR: 0.9, p=0.582). The median progression-free survival (PFS) was significantly longer for DaraRd (29.8 vs 22.5 months; p=0.028). DaraRd was better tolerated, registering a lower rate of grade 3-4 non-hematological toxicity (OR: 0.4, p.