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. 2023 Jul 25;7(14):3582-3591.
doi: 10.1182/bloodadvances.2022009311.

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

Srdan Verstovsek  1 , Ruben Mesa  2 , Vikas Gupta  3 , David Lavie  4 , Viviane Dubruille  5 , Nathalie Cambier  6 , Uwe Platzbecker  7 , Marek Hus  8 , Blanca Xicoy  9 , Stephen T Oh  10 , Jean-Jacques Kiladjian  11 , Alessandro M Vannucchi  12 , Aaron Gerds  13 , Miklos Egyed  14 , Jiří Mayer  15   16 , Tomasz Sacha  17 , Jun Kawashima  18 , Marc Morris  18 , Mei Huang  18 , Claire Harrison  19
Affiliations

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

Srdan Verstovsek et al. Blood Adv. .

Abstract

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).

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Conflict of interest statement

Conflict-of-interest disclosure: S.V. reports consulting fees from Bristol Myers Squibb/Celgene, Incyte, Novartis, and Sierra Oncology, and research funding from AstraZeneca, Blueprint Medicines, Bristol Myers Squibb/Celgene, CTI Biopharma, Genentech, Gilead, Incyte, Italfarmaco, Novartis, NS Pharma, PharmaEssentia, and Promedior. R.M. reports grants or contracts from AbbVie, Celgene, CTI Biopharma, Constellation Biopharma, Genotech, Incyte, Promedior, Samus Therapeutics, and the Mays Cancer Center P30 Cancer center support grant from the National Cancer Institute (CA054174), and consulting fees from Constellation Biopharma, LaJolla, Novartis, and Sierra Oncology. V.G. reports consulting fees from AbbVie, Bristol Myers Squibb/Celgene, Constellation Biopharma, Novartis, Pfizer, and Sierra Oncology; honoraria from Bristol Myers Squibb/Celgene, Constellation Biopharma, and Novartis; and participation in the data safety monitoring board or advisory board for AbbVie, Bristol Myers Squibb/Celgene, Pfizer, and Roche. V.D. reports grants from AbbVie and Novartis, and payment from Novartis, and attended meetings for AbbVie, Pfizer, and Novartis. U.P. reports consulting fees from AbbVie, Bristol Myers Squibb/Celgene, Janssen, and Novartis; honoraria from Amgen, Jazz Pharmaceuticals, and Takeda; and participation on data safety monitoring board or adviser board for AbbVie and Novartis. S.T.O. reports consulting fees from AbbVie, Blueprint Medicines, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, CTI Biopharma, Disc Medicine, Incyte, Kartos Therapeutics, PharmaEssentia, and Sierra Oncology. J.-J.K. reports honoraria from Novartis, and participation on a data safety monitoring board or advisory board for AbbVie, AOP Orphan, Bristol Myers Squibb, Incyte, and Novartis. A.M.V. reports honoraria from AbbVie, Blueprint Medicines, Bristol Myers Squibb, GSK, Incyte, and Novartis, and participation on a data safety monitoring board or advisory board for AbbVie, Blueprint Medicines, Bristol Myers Squibb, GSK, Incyte, MorphoSys, Novartis, and Roche. A.G. reports consulting fees from AbbVie, Bristol Myers Squibb, Constellation/MorphoSys, CTI Biopharma, Novartis, PharmaEssentia, and Sierra Oncology. J.M. reports research support from Sierra Oncology. T.S. reports honoraria from Angelini Pharma, Bristol Myers Squibb/Celgene, Novartis, Pfizer, and Roche. J.K., M.M., and M. Huang report employment and stock or stock options at Sierra Oncology. C.H. reports grant support from Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, and Novartis; consulting fees from AOP, Galecto, Keros, and Roche; honoraria from AbbVie, Celgene, Constellation Pharmaceuticals, CTI Biopharma, Janssen, and Novartis; participation in the data safety monitoring board or advisory board for AbbVie, AOP, CTI Biopharma, Geron, Promedior, Roche, and Sierra Oncology; and leadership or fiduciary role in the European Hematology Association and MPN Voice. The remaining authors declare no competing financial interests.

Figures

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Graphical abstract
Figure 1.
Figure 1.
Mean laboratory values over time based on treatment group. (A) Hemoglobin levels. (B) Platelet counts. (C) Neutrophil counts. DAN, danazol; MMB, momelotinib; OL/EXT, open-label/extended treatment; RUX, ruxolitinib; S1, SIMPLIFY-1; S2, SIMPLIFY-2.
See this image and copyright information in PMC

References

    1. Reilly JT, McMullin MF, Beer PA, et al. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012;158(4):453–471. - PubMed
    1. Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021;96(1):145–162. - PubMed
    1. Mesa R, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients' overall health and productivity: the MPN Landmark survey. BMC Cancer. 2016;16:167. - PMC - PubMed
    1. O'Sullivan JM, Harrison CN. Myelofibrosis: clinicopathologic features, prognosis, and management. Clin Adv Hematol Oncol. 2018;16(2):121–131. - PubMed
    1. Talpaz M, Kiladjian JJ. Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis. Leukemia. 2021;35(1):1–17. - PMC - PubMed

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