Momelotinib long-term safety and survival in myelofibrosis:
integrated analysis of phase 3 randomized controlled trials

J 2023

Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials

VERSTOVSEK, Srdan, Ruben MESA, Vikas GUPTA, David LAVIE, Viviane DUBRUILLE et. al.

Basic information

Original name

Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials

Authors

VERSTOVSEK, Srdan, Ruben MESA, Vikas GUPTA, David LAVIE, Viviane DUBRUILLE, Nathalie CAMBIER, Uwe PLATZBECKER, Marek HUS, Blanca XICOY, Stephen T OH, Jean-Jacques KILADJIAN, Alessandro M VANNUCCHI, Aaron GERDS, Miklos EGYED, Jiří MAYER (203 Czech Republic, belonging to the institution), Tomasz SACHA, Jun KAWASHIMA, Marc MORRIS, Mei HUANG and Claire HARRISON

Edition

Blood advances, AMSTERDAM, ELSEVIER, 2023, 2473-9529

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.500 in 2022

RIV identification code

RIV/00216224:14110/23:00132496

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1182/bloodadvances.2022009311

UT WoS

001041797400001

Keywords in English

Mastocytosis

Abstract

V originále

Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY 2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for >5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment emergent adverse event (AE) occurring in >20% of patients was diarrhea (any grade, 27% and grade >3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity. These trials were registered at www. clinicaltrials.gov as: MOMENTUM (#NCT04173494), SIMPLIFY-1 (#NCT01969838), SIMPLIFY-2 (#NCT02101268), and XAP (#NCT03441113).

Citovat

VERSTOVSEK, Srdan, Ruben MESA, Vikas GUPTA, David LAVIE, Viviane DUBRUILLE, Nathalie CAMBIER, Uwe PLATZBECKER, Marek HUS, Blanca XICOY, Stephen T OH, Jean-Jacques KILADJIAN, Alessandro M VANNUCCHI, Aaron GERDS, Miklos EGYED, Jiří MAYER, Tomasz SACHA, Jun KAWASHIMA, Marc MORRIS, Mei HUANG and Claire HARRISON. Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. Blood advances. AMSTERDAM: ELSEVIER, 2023, vol. 7, No 14, p. 3582-3591. ISSN 2473-9529. Available from: https://dx.doi.org/10.1182/bloodadvances.2022009311.

@article{2348886,
   author = {Verstovsek, Srdan and Mesa, Ruben and Gupta, Vikas and Lavie, David and Dubruille, Viviane and Cambier, Nathalie and Platzbecker, Uwe and Hus, Marek and Xicoy, Blanca and Oh, Stephen T and Kiladjian, JeanandJacques and Vannucchi, Alessandro M and Gerds, Aaron and Egyed, Miklos and Mayer, Jiří and Sacha, Tomasz and Kawashima, Jun and Morris, Marc and Huang, Mei and Harrison, Claire},
   article_location = {AMSTERDAM},
   article_number = {14},
   doi = {http://dx.doi.org/10.1182/bloodadvances.2022009311},
   keywords = {Mastocytosis},
   language = {eng},
   issn = {2473-9529},
   journal = {Blood advances},
   title = {Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials},
   url = {https://www.sciencedirect.com/science/article/pii/S2213219823002258},
   volume = {7},
   year = {2023}
}

TY  - JOUR
ID  - 2348886
AU  - Verstovsek, Srdan - Mesa, Ruben - Gupta, Vikas - Lavie, David - Dubruille, Viviane - Cambier, Nathalie - Platzbecker, Uwe - Hus, Marek - Xicoy, Blanca - Oh, Stephen T - Kiladjian, Jean-Jacques - Vannucchi, Alessandro M - Gerds, Aaron - Egyed, Miklos - Mayer, Jiří - Sacha, Tomasz - Kawashima, Jun - Morris, Marc - Huang, Mei - Harrison, Claire
PY  - 2023
TI  - Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials
JF  - Blood advances
VL  - 7
IS  - 14
SP  - 3582-3591
EP  - 3582-3591
PB  - ELSEVIER
SN  - 24739529
KW  - Mastocytosis
UR  - https://www.sciencedirect.com/science/article/pii/S2213219823002258
N2  - Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY 2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for >5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment emergent adverse event (AE) occurring in >20% of patients was diarrhea (any grade, 27% and grade >3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity. These trials were registered at www. clinicaltrials.gov as: MOMENTUM (#NCT04173494), SIMPLIFY-1 (#NCT01969838), SIMPLIFY-2 (#NCT02101268), and XAP (#NCT03441113).
ER  -

VERSTOVSEK, Srdan, Ruben MESA, Vikas GUPTA, David LAVIE, Viviane DUBRUILLE, Nathalie CAMBIER, Uwe PLATZBECKER, Marek HUS, Blanca XICOY, Stephen T OH, Jean-Jacques KILADJIAN, Alessandro M VANNUCCHI, Aaron GERDS, Miklos EGYED, Jiří MAYER, Tomasz SACHA, Jun KAWASHIMA, Marc MORRIS, Mei HUANG and Claire HARRISON. Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. \textit{Blood advances}. AMSTERDAM: ELSEVIER, 2023, vol.~7, No~14, p.~3582-3591. ISSN~2473-9529. Available from: https://dx.doi.org/10.1182/bloodadvances.2022009311.

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