TY - JOUR
T1 - Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis
AU - Mesa, Ruben
AU - Harrison, Claire
AU - Oh, Stephen T.
AU - Gerds, Aaron T.
AU - Gupta, Vikas
AU - Catalano, John
AU - Cervantes, Francisco
AU - Devos, Timothy
AU - Hus, Marek
AU - Kiladjian, Jean Jacques
AU - Lech-Maranda, Ewa
AU - McLornan, Donal
AU - Vannucchi, Alessandro M.
AU - Platzbecker, Uwe
AU - Huang, Mei
AU - Strouse, Bryan
AU - Klencke, Barbara
AU - Verstovsek, Srdan
N1 - Funding Information:
Momelotinib is sponsored by Sierra Oncology. Lynn M. Neilson, PhD, a medical writer employed by Sierra Oncology, provided written drafts and editorial assistance to the authors during preparation of this manuscript. Editorial support was provided by BluPrint Oncology.
Funding Information:
Momelotinib is sponsored by Sierra Oncology. Lynn M. Neilson, PhD, a medical writer employed by Sierra Oncology, provided written drafts and editorial assistance to the authors during preparation of this manuscript. Editorial support was provided by BluPrint Oncology.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/9
Y1 - 2022/9
N2 - Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p < 0.0001) and multivariate (HR = 0.311; p < 0.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib’s pro-erythropoietic mechanism of action, and potentially informing treatment decision-making.
AB - Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p < 0.0001) and multivariate (HR = 0.311; p < 0.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib’s pro-erythropoietic mechanism of action, and potentially informing treatment decision-making.
UR - http://www.scopus.com/inward/record.url?scp=85134685233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134685233&partnerID=8YFLogxK
U2 - 10.1038/s41375-022-01637-7
DO - 10.1038/s41375-022-01637-7
M3 - Article
C2 - 35869266
AN - SCOPUS:85134685233
SN - 0887-6924
VL - 36
SP - 2261
EP - 2268
JO - Leukemia
JF - Leukemia
IS - 9
ER -