Ruben A. Mesa, MD, executive director, Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, discusses the rationale for the phase 3 MOMENTUM study (NCT04173494) in myelofibrosis.

MOMENTUM examined the efficacy of momelotinib vs danazol in patients with primary myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocytopenia myelofibrosis with symptomatic disease and anemia.

This study was meant to enhance the understanding of the impact of momelotinib in this patient population, Mesa says. The prior phase 3 Simplify 1 trial (NCT01969838) had examined momelotinib in the frontline setting vs ruxolitinib (Jakafi).

MOMENTUM aimed to target patients who had significant anemia and symptoms, and who had previously failed on ruxolitinib, Mesa adds. The primary goal of MOMENTUM was to improve symptoms, with secondary end points of improved splenic response and transfusion independence, against the current standard of care, danazol.

On the trial, 195 patients were randomized 2:1 between momelotinib once daily at standard 200 mg vs danazol, Mesa continues. The placebo-controlled study allowed subsequent crossover for patients to receive momelotinib, Mesa concludes.

Videos

Ruben A. Mesa, MD, discusses the rationale for the phase 3 MOMENTUM study in myelofibrosis.


Dr. Mesa on the Rationale for the MOMENTUM Trial in Myelofibrosis

Ruben A. Mesa, MD, executive director, Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, discusses the unique characteristics of momelotinib in myelofibrosis. 

Momelotinib is an investigational JAK inhibitor that has demonstrated efficacy in patients with myelofibrosis, Mesa says. The approved JAK inhibitors ruxolitinib (Jakafi) and fedratinib (Inrebic) have demonstrated utility in reducing spleen size and improving symptom burden; however, they do not improve and can worsen anemia, Mesa explains. 

Conversely, momelotinib has been shown to improve anemia, so the agent could fulfill an unmet need in myelofibrosis, Mesa says. In addition to JAK1/2, momelotinib inhibits ACVR1, which inhibits inflammation and hepcidin and could explain how the agent improves anemia.

Ongoing clinical trials, such as the phase 3 MOMENTUM trial (NCT04173494), are evaluating the extent to which momelotinib can improve splenomegaly, symptom burden, and anemia, Mesa concludes. 

Ruben A. Mesa, MD, discusses the unique characteristics of momelotinib in myelofibrosis.  



Dr. Mesa on the Unique Characteristics of Momelotinib in Myelofibrosis 

Ruben Mesa, MD, discusses data from the following presentation:

Transfusion Independence Is Associated With Improved Overall Survival in Myelofibrosis Patients Receiving Momelotinib (Mesa R, EHA 2021, Abstract S202)

The objective of this study is to report data from patients with myelofibrosis treated with the JAK1, JAK2, and ACVR1/ALK2 inhibitor momelotinib in the SIMPLIFY-1 and SIMPLIFY-2 trials:

SIMPLIFY-1: momelotinib (MMB) vs ruxolitinib (RUX) in JAK inhibitor-naïve patients (NCT01969838)

SIMPLIFY-2: MMB vs best available therapy (BAT; RUX in 88% of patients) in patients with prior JAK inhibitor (ruxolitinib) therapy (NCT02101268)

Transfusion independence (TI) response rates were higher for MMB compared with BAT/RUX in both SIMPLIFY-1 (67% vs 49%) and SIMPLIFY-2 (43% vs 21%).

The week 24 TI response was higher in patients randomly assigned to MMB vs RUX, regardless of baseline anemia, platelet count, or transfusion status.

In SIMPLIFY-1, median overall survival (OS) was found to be 53.1 months in the RUX to MMB crossover arm compared with the MMB to MMB arm, where OS was not reached. In SIMPLIFY-2, median overall survival was 37.5 months in BAT/RUX to MMB arm vs 34.3 months in MMB to MMB arm.

SIMPLIFY-1: 3-year survival in MMB TI responders was 80% compared with 50% in MMB TI nonresponders (HR, 0.30; 

< .0001); similar results are found for patients with anemia who are week 24 MMB TI responders.

SIMPLIFY-2: Patients randomized to MMB who were TI responders at week 24 show a trend toward better OS compared with TI nonresponders (HR, 0.52; 

Ruben Mesa, MD, Director of UT Health San Antonio MD Anderson Cancer Center, presents data from the 2021 European Hematology Association Virtual Congress from the SIMPLIFY-1 and SIMPLIFY-2 trials of patients with myelofibrosis who were treated with momelotinib.

Ruben Mesa, MD, UT Health San Antonio Cancer Center

Articles

Dr. Mesa on the Rationale for the MOMENTUM Trial in Myelofibrosis

Dr. Mesa on the Unique Characteristics of Momelotinib in Myelofibrosis

Rapid Readouts: SIMPLIFY-1 and SIMPLIFY-2 Trials