Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study

Haematologica. 2023 Aug 31. doi: 10.3324/haematol.2023.283509. Online ahead of print.ABSTRACTMelphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23, 2022 (data cutoff date). In total, 54 of 240 planned patients were randomized (melflufen group, n=27; daratumumab group, n=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (hazard ratio, 0.18 [95% confidence interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grad...

Source: Haematologica - August 30, 2023 Category: Hematology Authors: Lud ěk Pour Monika Szarejko Jelena Bila Fredrik H Schjesvold Ivan Spicka Vladimir Maisnar Artur Jurczyszyn Zhanet Grudeva-Popova Roman H ájek Ganna Usenko Marcus Thuresson Stefan Norin Sara Jarefors Nicolaas A Bakker Paul G Richardson Maria-Victoria Mat Source Type: research