TY - JOUR
T1 - Momelotinib long-term safety and survival in myelofibrosis
T2 - integrated analysis of phase 3 randomized controlled trials
AU - Verstovsek, Srdan
AU - Mesa, Ruben
AU - Gupta, Vikas
AU - Lavie, David
AU - Dubruille, Viviane
AU - Cambier, Nathalie
AU - Platzbecker, Uwe
AU - Hus, Marek
AU - Xicoy, Blanca
AU - Oh, Stephen T.
AU - Kiladjian, Jean Jacques
AU - Vannucchi, Alessandro M.
AU - Gerds, Aaron
AU - Egyed, Miklos
AU - Mayer, Jiří
AU - Sacha, Tomasz
AU - Kawashima, Jun
AU - Morris, Marc
AU - Huang, Mei
AU - Harrison, Claire
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology.
PY - 2023/7/25
Y1 - 2023/7/25
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164938795&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2022009311
DO - 10.1182/bloodadvances.2022009311
M3 - Article
C2 - 37042865
AN - SCOPUS:85164938795
SN - 2473-9529
VL - 7
SP - 3582
EP - 3591
JO - Blood Advances
JF - Blood Advances
IS - 14
ER -