Transfusion Independence Linked with Improved Survival in SIMPLIFY Trials

Transfusion independence was associated with improved survival in the SIMPLIFY-1 and SIMPLIFY-2 trials of momelotinib in patients with myelofibrosis.

Ruben Mesa, MD, FACP, of the UT Health San Antonio MD Anderson Cancer Center, and colleagues conducted the study because Janus kinase (JAK) inhibitors approved for myelofibrosis “provide spleen and symptom improvements but do not address anemia, a negative prognostic factor.”

Dr. Mesa and colleagues collected mature overall survival (OS) and leukemia-free survival (LFS) from the phase III SIMPLFIY trials, in which momelotinib, an inhibitor of ACVR1/ALK2, JAK1, and JAK2 showed activity against symptoms, anemia, and splenomegaly. The researchers conducted retrospective analyses of patient baseline characteristics and efficacy endpoints to assess associations with OS.

In the SIMFLIY-1 trial, patients who were naïve to JAK inhibitors and were randomized to receive momelotinib or ruxolitinib then momelotinib had similar OS distributions (hazard ratio [HR], 1.02; 95% CI, 0.73-1.43), as well as LFS distributions (HR, 1.08; 95% CI, 0.78-1.50).

The two-year OS rate was 81.6% in patients receiving momelotinib, while it was 80.6% in patients receiving ruxolitinib then momelotinib. The two-year LFS rate was 80.7% in patients receiving momelotinib, while it was 79.3% in patients receiving ruxolitinib then momelotinib.

In ruxolitinib-exposed patients in the SIMPLIFY-2 trial, the two-year OS rate was 65.8% in those receiving momelotinib, while it was 61.2% in those receiving the best available therapy followed by momelotinib (HR, 0.98; 95% CI, 0.59-1.62). The two-year LFS rate was 64.2% in patients receiving momelotinib and 59.7% in those receiving the best available therapy followed by momelotinib (HR, 0.97; 95% CI, 0.59-1.60).

Baseline transfusion independence was significantly associated with improved survival in the SIMPLIFY-1 trial (HR, 0.474, P=.0001) and in the SIMPLIFY-2 trial (HR, 0.226; P=.0005). The transfusion independence response at week 24 in JAK inhibitor-naïve patients who received momelotinib was significantly associated with improved OS in a univariate analysis (HR, 0.323; P<.0001), as well as a multivariate analysis (HR, 0.311; P<.0001)

“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,” Dr. Mesa and colleagues concluded.

Reference

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. 2022;36(9):2261-2268. doi:10.1038/s41375-022-01637-7