Dr. Kuykendall on the Evaluation of Momelotinib in Myelofibrosis

Andrew Kuykendall, MD, assistant member, the Department of Malignant Hematology, Moffitt Cancer Center, discusses the evaluation of momelotinib in patients with symptomatic and anemic myelofibrosis.

Momelotinib has demonstrated clinical benefit in the phase 3 SIMPLIFY 1 (NCT01969838) and SIMPLIFY 2 (NCT02101268) trials. SIMPLIFY 1, which evaluated momelotinib vs ruxolitinib (Jakafi), met its primary end point, showing that momelotinib was noninferior to ruxolitinib. The splenic response rates were 26.5% for momelotinib and 29% for ruxolitinib. SIMPLIFY 2 trial evaluated momelotinib vs best available therapy in anemic or thrombocytopenic patients with myelofibrosis. Although SIMPLIFY 2 produced a 26% total symptom score (TSS) response, spleen volume reductions of at least 35% were not achieved with momelotinib, prompting investigators to designed third phase 3 trial.

The phase 3 MOMENTUM trial (NCT04173494) evaluated momelotinib vs danazol in order to better identify patients who may derive a clinical benefit from momelotinib. The trial enrolled patients that had big spleens, had symptoms of anemia, and received prior treatment with ruxolitinib in some fashion but experienced toxicity or did not experience a full response, Kuykendall explains.

Danazol has been used in practice for patients with anemic myelofibrosis, and the study used TSS response, spleen response, and transfusion independence as key end points. Findings from MOMENTUM showed that momelotinib was associated with better TSS responses and spleen responses, as well as noninferiority in transfusion independence, compared with danazol, Kuykendall says.

The 24-week TSS response rate was 24.6% for momelotinib, compared with 9.2% for danazol. Additionally, 40% of patients in the momelotinib arm had a spleen volume reduction of at least 25%, and 23.1% experienced at least a 35% spleen volume reduction. In the danazol arm, those rates were 6.2% and 3.1%, respectively. Additionally, 31% of patients in the momelotinib arm were transfusion independent at week 24, vs 20% of patients in the danazol arm.