Hemoglobin Improvement With Momelotinib Confers OS Benefit in Myelofibrosis With Anemia

Achievement of hemoglobin levels greater than 10 g/dL with momelotinib (Ojjaara) is a positive prognostic factor in patients with myelofibrosis regardless of baseline anemia severity and supports the treatment goal of early anemia intervention in this population, according to Francesca Palandri, MD, PhD.

Findings from the phase 3 SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials supported the 2023 FDA approval of momelotinib for the treatment of adult patients with intermediate- or high-risk myelofibrosis and anemia.1 These trials showed the efficacy of momelotinib regarding spleen response, symptom response, and anemia-related benefits. However, there is a lack of data regarding the timing of anemia-related improvements achieved with momelotinib, and the effects of improving hemoglobin levels in patients with baseline moderate-to-severe anemia has historically not been characterized.

Therefore, Palandri and co-investigators conducted a post hoc analysis of SIMPLIFY-1 and MOMENTUM to gain insights on the kinetics and survival effects of momelotinib-induced hemoglobin level improvements.2 In the SIMPLIFY-1 cohort (n = 86), 69% of patients with moderate anemia at baseline and 50% of patients with severe anemia at baseline achieved hemoglobin levels greater than 10 g/dL by week 24. These respective rates in the MOMENTUM cohort (n = 126) were 47% and 24%. In both trial populations, patients with baseline moderate anemia had a numerically faster time to achieving hemoglobin levels greater than 10 g/dL than those with baseline severe anemia. Furthermore, achievement of hemoglobin levels of higher than 10 g/dL by week 24 was associated with improved overall survival (OS) irrespective of baseline anemia severity or prior JAK inhibitor experience in both trial populations.

“If we want to optimize the clinical benefit with momelotinib, it is important to start the treatment early, possibly in the frontline setting, and possibly when anemia is only moderate and not severe,” Palandri said in an interview with OncLive®.

In the interview, Palandri discussed the MOMENTUM trial design, data from each trial population of the post hoc analysis, and how these data may influence clinical practice.

She highlighted the SIMPLIFY-1 trial design and findings from a subgroup analysis of this trial investigating the clinical relevance of achieving spleen response and transfusion independence in another article.

Palandri is a medical doctor and an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Italy.

OncLive: What was the design of the MOMENTUM trial, and how did it differ from SIMPLIFY-1?

Palandri: Importantly, MOMENTUM was a clinical trial that was completely different from the SIMPLIFY-1 trial. In the MOMENTUM trial, we focused only on patients with hemoglobin levels below 10, so this [trial had] clear [enrollment criteria] for anemic patients. These patients were randomly assigned to receive either momelotinib or danazol [Danocrine], which was the standard of care for patients with anemia. Additionally, in the MOMENTUM trial, most of the patients were included after progression on a previous JAK inhibitor. We are talking about a more complex population who received momelotinib mostly in the second-line setting.

What was the rationale for conducting the post hoc analysis of hemoglobin improvement in MOMENTUM and SIMPLIFY-1, and what were the key findings?

This post hoc analysis focused on the patients who started momelotinib plus ruxolitinib with hemoglobin levels less than 10 g/dL. We wanted to understand the dynamics of hemoglobin levels to see how many patients could reach a hemoglobin level higher than 10 g/dL by week 24.

In the SIMPLIFY-1 trial, we observed that 69% of the patients who started with baseline hemoglobin levels between 8 g/dL and 10 g/dL—what we call moderate anemia—achieved levels of hemoglobin at week 24 that were higher than 10 g/dL. This percentage of responders decreased to 50% [in patients who] started momelotinib with hemoglobin levels less than 8 g/dL, which means severe anemia. Additionally, the time to achieve these hemoglobin levels was a bit longer for the patients who started [treatment when they had] severe anemia compared with the patients who started [treatment when they had] moderate anemia.

We observed pretty much the same results in the second-line setting in the MOMENTUM trial. However, we also observed a decrease in the rate of responses, with 47% of patients who [started treatment when they had] moderate anemia having hemoglobin levels higher than 10 g/dL by week 24 and 24% of patients [who started treatment when they had] severe anemia having hemoglobin levels higher than 10 g/dL by week 24. Additionally, in the MOMENTUM trial, we observed a delayed response for the patients starting [treatment when they had] severe anemia.

What are the potential future implications of these findings?

Importantly, achieving a hemoglobin level higher than 10 g/dL by week 24 is important for the survival of our patients. We performed an OS analysis, and we stratified the patients according to whether they could achieve a hemoglobin level higher than 10 g/dL by week 24 with momelotinib. For the patients achieving higher hemoglobin levels, the survival was prolonged. This is a key message to bring to the audience because it correlates the ability to reverse anemia with the possibility to increase the survival of our patients.

References

Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed July 30, 2025. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia

Palandri F, O’Connell C, Vachhani P, et al. Survival impact and kinetics of hemoglobin improvement with momelotinib in patients with myelofibrosis and moderate to severe anemia: post hoc analyses of SIMPLIFY-1 and MOMENTUM. Presented at: 2025 EHA Congress. June 12-15, 2025; Milan, Italy. Abstract PF828.