Momelotinib Associated With Positive Survival Outcomes in Patients With Myelofibrosis: SIMPLIFY Trials

Momelotinib demonstrated clinical efficacy improving overall survival (OS) and leukemia-free survival (LFS) in patients with myelofibrosis, according to findings from the 2 phase 3 SIMPLIFY trials.

“Janus kinase [JAK] inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of activin A receptor type 1 (ACVR1)/activin-receptor-like kinase-2 (ALK2), JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials,” wrote Ruben Mesa, MD, UT Health San Antonio Cancer Center, TX, and colleagues.

The SIMPLIFY-1 and SIMPLIFY-2 trials investigated momelotinib in >1000 patients with myelofibrosis, including in JAK inhibitor-naïve patients (SIMPLIFY-1) and previously ruxolitinib-exposed patients (SIMPLIFY-2). This updated analysis reports mature OS and LFS findings from both of these studies. In addition, Dr Mesa and colleagues report on retrospective analyses of baseline characteristics and efficacy end points for OS associations.

In the SIMPLIFY-1 trial, OS was similar between JAK inhibitor-naïve patients randomized to momelotinib or ruxolitinib then momelotinib (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.73 to 1.43). In addition, LFS was similar between the 2 groups (HR, 1.08; 95% CI, 0.78 to 1.50). The 2-year OS and LFS were 81.6% and 80.7%, respectively, with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib.

In the SIMPLIFY-2 trial, the 2-year OS and LFS in ruxolitinib-exposed patients randomized to momelotinib or ruxolitinib then momelotinib were 65.8% and 64.2%, respectively, with momelotinib (OS HR, 0.98; 95% CI, 0.59 to 1.62) and 61.2% and 59.7% with best available therapy then momelotinib (LFS HR, 0.97; 95% CI, 0.59 to 1.60).

Findings from the retrospective analyses of baseline characteristics showed that baseline transfusion independence was associated with improved survival in both SIMPLIFY-1 (HR, 0.474; P = .0001) and SIMPLIFY-2 (HR, 0.226; P = .0005). At 24 weeks, transfusion independence response was associated with improved OS in univariate (HR, 0.323; P <.0001) and multivariate (HR, 0.311; P <.0001) analyses in JAK inhibitor-naïve patients randomized to momelotinib.

“These findings underscore the importance of achieving or maintaining [transfusion independence] in myelofibrosis, supporting the clinical relevance of momelotinib's pro-erythropoietic mechanism of action, and potentially informing treatment decision-making,” the study authors concluded.

“Momelotinib’s anemia benefits are currently being further characterized in MOMENTUM (NCT04173494), a global phase 3 clinical trial in symptomatic and anemic patients previously treated with an approved JAK [inhibitor], intended to support potential registration of momelotinib for the treatment of [myelofibrosis],” they added.

Source:

Mesa R, Harrison C, Oh ST, et al. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis. Leukemia. Published online July 22, 2022. doi:10.1038/s41375-022-01637-7