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

J 2024

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 et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{2417620,
   author = {Pour, Luděk and Szarejko, Monika and Bila, Jelena and Schjesvold, Fredrik H and Spicka, Ivan and Maisnar, Vladimir and Jurczyszyn, Artur and GrudevaandPopova, Zhanet and Hajek, Roman and Usenko, Ganna and Thuresson, Marcas and Norin, Stefan and Jarefors, Sara and Bakker, Nicolaas A and Richardson, Paul G and Mateos, MariaandVictoria},
   article_location = {PAVIA},
   article_number = {3},
   doi = {http://dx.doi.org/10.3324/haematol.2023.283509},
   keywords = {melflufen; daratumumab; dexamethasone; multiple myeloma},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study},
   url = {https://haematologica.org/article/view/haematol.2023.283509},
   volume = {109},
   year = {2024}
}

TY  - JOUR
ID  - 2417620
AU  - Pour, Luděk - Szarejko, Monika - Bila, Jelena - Schjesvold, Fredrik H - Spicka, Ivan - Maisnar, Vladimir - Jurczyszyn, Artur - Grudeva-Popova, Zhanet - Hajek, Roman - Usenko, Ganna - Thuresson, Marcas - Norin, Stefan - Jarefors, Sara - Bakker, Nicolaas A - Richardson, Paul G - Mateos, Maria-Victoria
PY  - 2024
TI  - Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study
JF  - Haematologica
VL  - 109
IS  - 3
SP  - 895-905
EP  - 895-905
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - melflufen
KW  - daratumumab
KW  - dexamethasone
KW  - multiple myeloma
UR  - https://haematologica.org/article/view/haematol.2023.283509
N2  - 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.
ER  -

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. \textit{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.

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