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

POUR, Luděk, Monika SZAREJKO, Jelena BILA, Fredrik H SCHJESVOLD, Ivan SPICKA, Vladimir MAISNAR, Artur JURCZYSZYN, Zhanet GRUDEVA-POPOVA, Roman HAJEK, Ganna USENKO, Marcas THURESSON, Stefan NORIN, Sara JAREFORS, Nicolaas A BAKKER, Paul G RICHARDSON and Maria-Victoria MATEOS. 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. PAVIA: FERRATA STORTI FOUNDATION, 2024, vol. 109, No 3, p. 895-905. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2023.283509.

Basic information

• Original name: Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study
• Authors: POUR, Luděk (203 Czech Republic, belonging to the institution), Monika SZAREJKO, Jelena BILA, Fredrik H SCHJESVOLD, Ivan SPICKA, Vladimir MAISNAR, Artur JURCZYSZYN, Zhanet GRUDEVA-POPOVA, Roman HAJEK, Ganna USENKO, Marcas THURESSON, Stefan NORIN, Sara JAREFORS, Nicolaas A BAKKER, Paul G RICHARDSON and Maria-Victoria MATEOS.
• Edition: Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2024, 0390-6078.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30205 Hematology
• Country of publisher: Italy
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 10.100 in 2022
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.3324/haematol.2023.283509
• UT WoS: 001182209400032
• Keywords in English: melflufen; daratumumab; dexamethasone; multiple myeloma
• Tags: 14110212, rivok
• Tags: International impact, Reviewed

Abstract

Melphalan 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 immu- nomodulatory 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 23rd 2022 (data cut-off 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 grade >= 3 treatment -emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies.