Momelotinib Improves Transfusion Independence Rates Vs Ruxolitinib in Anemic, JAK Inhibitor–Naïve Myelofibrosis

Momelotinib could represent a promising treatment option for patients with myelofibrosis who are both JAK inhibitor–naïve and anemic, irrespective of baseline platelet count or transfusion status, according to Jean-Jacques Kiladjian, MD, PhD.

Results from an analysis presented during the 2021 ASCO Annual Meeting, which examined data from the phase 3 SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) trials, showed that 24-week transfusion independence rates were significantly higher with momelotinib vs ruxolitinib (Jakafi) in patients with anemia, regardless of the degree of anemia. Moreover, momelotinib also elicited superior efficacy in both achieving and maintaining transfusion independence in those patients who are JAK inhibitor naïve, regardless of platelet counts or transfusions status at baseline.

“This research [provided insight into how we might decide] which JAK inhibitor is better suited for a certain patient population,” Kiladjian said. “For example, for patients with severe thrombocytopenia who may not benefit from a maximum dose of ruxolitinib, momelotinib may be the best treatment [option] for them. Conversely, for patients with high platelet counts, no superiority was seen with momelotinib; therefore, ruxolitinib may be the first choice.”

In an interview with OncLive^®, Kiladjian, professor of Clinical Pharmacology at Paris Diderot University, discussed the effectiveness of momelotinib compared with ruxolitinib in patients with myelofibrosis who have anemia and are naïve to JAK inhibitors.

OncLive^®: What was the rationale to further analyze transfusion independence rates by baseline platelet levels and transfusion status in patients enrolled to the SIMPLIFY-1 and SIMPLIFY-2 trials?

Kiladjian: Momelotinib is a dual inhibitor of JAK1 and JAK2, but [also of] ACVR1, which is another target of interest, especially in patients with anemia. ACVR1 is a receptor involved in hepcidin metabolism and induces an erythropoietic response in patients with myelofibrosis. This background was the rationale for specifically targeting patients with myelofibrosis who have anemia and who are transfusion dependent or independent. [Additionally, we wanted to] test whether the drug could induce the same benefits, regardless of transfusion status, and examine other hematologic parameters, such as thrombocytopenia.

Could you briefly discuss the SIMPLIFY trials and their significance?

Momelotinib was tested in 2 different phase 3 randomized trials. [The first was the] SIMPLIFY-1 trial, which tested the drug in patients who were JAK inhibitor naïve, and the second was the SIMPLIFY-2 trial, which examined the drug in patients who had previously received treatment with a JAK inhibitor, mostly ruxolitinib, and proved to be resistant or intolerant to that therapy.

We analyzed the responses in both studies to see whether they were different in patients who were primarily treated with momelotinib vs those who received the agent in the second-line setting.

What were some of the key findings from the analysis?

The most important finding was the confirmation that response in terms of transfusion independence was observed in every type of patient, regardless of their baseline platelet count. This is relevant, especially when compared with ruxolitinib, because that agent has some toxicity in terms of platelets and worsens thrombocytopenia. We often need to reduce the dose of ruxolitinib or stop treatment in patients who are thrombocytopenic, which means we lose efficacy, both in spleen response and anemia response. In contrast, we observed that we could maintain a good dose level for patients treated in the momelotinib arms of both studies, and therefore, [we could] achieve a significant impact with the drugs on spleen response and transfusion independence.

Were any unexpected safety signals observed?

We did not observe new toxicity findings compared with those that were already well known from the SIMPLIFY-1 and SIMPLIFY-2 studies.

Reference

1. Kiladjian J, Platzbecker U, Mayer J, et al. Improved transfusion independence rates for momelotinib versus ruxolitinib in anemic JAKi naïve myelofibrosis patients independent of baseline platelet or transfusion status. J Clin Oncol. 2021;39(15):e19039. doi:10.1200/JCO.2021.39.15_suppl.e19039