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 a 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, roč. 109, č. 3, s. 895-905. ISSN 0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2023.283509.

Základní údaje

• Originální název: Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study
• Autoři: POUR, Luděk (203 Česká republika, domácí), 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 a Maria-Victoria MATEOS.
• Vydání: Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2024, 0390-6078.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30205 Hematology
• Stát vydavatele: Itálie
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 10.100 v roce 2022
• Organizační jednotka: Lékařská fakulta
• Doi: http://dx.doi.org/10.3324/haematol.2023.283509
• UT WoS: 001182209400032
• Klíčová slova anglicky: melflufen; daratumumab; dexamethasone; multiple myeloma
• Štítky: 14110212, rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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.