For patients with myelofibrosis (MF) and anemia, momelotinib therapy demonstrated improved anemia symptoms and controlled splenomegaly, according to results presented by Lucía Pérez-Lamas, Hospital Universitario Puerta de Hierro, Madrid, Spain, at the 66^th ASH Annual Meeting in San Diego, California.

Standard treatment of MF has included Janus kinase inhibitor therapy, which may worsen anemia among patients. Momelotinib has been approved for the treatment of MF and demonstrated improved anemia symptoms in patients due to its ability to inhibit activin A receptor type 1, however, real-world data on its efficacy for patients with MF who had anemia. Researchers sought to determine the efficacy and safety of momelotinib for MF treatment among patients with anemia in an observational, retrospective study.

“Real-life treatment with MMB confirms its marked effect in improving anemia in MF patients, with high rates of patients achieving TI [transfusion independence] in both JAK-[inhibitor]-exposed and JAK-[inhibitor] naïve patients,” Pérez-Lamas and colleagues concluded, “additionally, [momelotinib] has proven effective in reducing symptoms and controlling splenomegaly in pts previously exposed to ruxolitinib, with an acceptable toxicity profile."

Transcript:

Hello, good morning. I'm Lucía Pérez-Lamas from Puerta de Hierro University Hospital, and I'm here at ASH to present the Spanish group experience on the real-world data on momelotinib use in myelofibrosis patients with anemia. So, as you know, momelotinib is a JAK1, JAK2, and ACVR1 inhibitor, but it has been recently approved. This drug has demonstrated clinical efficacy in controlling disease related symptoms and splenomegaly, but opposed to fedratinib and ruxolitinib, has also shown benefits in terms of anemia response. Due to its recent approval, real-world data on momelotinib use remains limited.

To give insights in this regard, we designed our retrospective observational multicenter study to study the efficacy and safety of momelotinib in a real-world cohort. We studied patients receiving momelotinib in a compassionate use program provided by GSK. To define anemia, we used the 2024 Revised Criteria for Anemia of the European LeukemiaNet and International Working Party and to assess splenomegaly we used the 2013 criteria of the ELN-IWG.

We've collected 154 patients receiving momelotinib in 74 centers in Spain. Median age was 72 years. Most of them had a high risk and intermediate-2 risk myelofibrosis. Median hemoglobin before start of momelotinib was 8 and 70% of patients were transfusion dependent prior to momelotinib start. It's important to remark that 23% of the patients received momelotinib as their first JAK inhibitor while 77% of patients were JAK inhibitor exposed.

Regarding symptoms improvement, of the symptomatic patients, 92% of the patients show an improvement. You can check specific symptoms improvement in the poster. In terms of anemia response, we saw an increase in hemoglobin level from 8 to 9.3 at 2 months, and that remained stable at 6 months of the patients that were transfusion dependent. We saw 48% of patients achieving transfusion independency at 3 months, and that same rate remain stable at 6, 9 and 12 months.

It's important to note that JAK exposed patients had greater improvements than the JAK naive patients. Regarding the group that remain transfusion dependent, the mean number of red blood cell units received per month decreased from 4 to 2.25. In terms of splenomegaly, we saw of the overall cohort around a 60% improvement with 25% of patients achieving the 2013 ELN-IWG criteria. It's important to remark that JAK-naive patients had a slightly greater improvement than JAK-exposed patients.

Regarding safety, the most frequent adverse events were thrombocytopenia, diarrhea, dizziness, nausea, and hepatotoxicity. Most frequent grade 3- 4 adverse events were thrombocytopenia with 6%, infections with 3%, and hepatotoxicity with 2.5%. After a median of 5.5 months, 79% of patients remain on treatment, reason for treatment discontinuations were 6 patients due toxicity, 5 due to lack of efficacy, and the rest discontinued due to transformation, progression or death.

To conclude, we saw a good efficacy profile in terms of anemia response with patients achieving high rates of transfusion independence, and we also saw efficacy in our real-world cohort in terms of disease related symptoms and splenomegaly, both in JAK-naive and JAK-exposed patients.

Source:

Pérez-Lamas L, Segura A, García R, et al. Real-world outcomes of momelotinib as an alternative therapy to other JAK inhibitors in myelofibrosis patients with anemia. Dec 7-10, 2024; San Diego, CA. Abstract: 1790