Transitioning to momelotinib from ruxolitinib (RUX) can swiftly improve anemia and shift patients to transfusion independence (TI) without compromising splenic control among patients with myelofibrosis (MF), according to a study published in Haematologica.
In the present study, researchers investigated the clinical outcomes associated with administering momelotinib right after stopping RUX without tapering or washout of RUX.
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The phase 3 SIMPLIFY-1 study involved 432 janus kinase inhibitor (JAKi)-naïve patients with MF randomized 1:1 to momelotinib or RUX. The patients received momelotinib at 200 mg once daily or ruxolitinib twice daily across 4 starting doses (5, 10, 15, and 20 mg twice daily) based on the baseline platelet levels and other laboratory values.
After the completion of the randomized treatment period of 24 weeks, patients were allowed to continue momelotinib, and patients randomized to RUX were allowed to cross over to the open-label momelotinib instantly, without tapering or washout for up to the 168th day.
The study analyzed clinical data, including spleen volume, transfusions, dosing, and hemoglobin levels (collected at weeks 4 and 8 after the crossover and every 12 weeks) to characterize the clinical outcomes after transitioning to momelotinib from RUX.
Study findings indicated that the reduction in mean spleen volume between RUX and momelotinib was not statistically different over the 24 weeks treatment duration. Moreover, the mean spleen volume was well maintained beyond week 24, while the mean hemoglobin levels improved rapidly after the transition from RUX to momelotinib.
“These analyses provide confidence in an immediate transition to momelotinib from ruxolitinib without washout or tapering, which is likely to rapidly improve anemia without compromising safety or control of symptoms and spleen,” the study authors added.
Additionally, the proportion of RUX-randomized patients with TI decreased from 70% at baseline to 49% at week 24, while 92 nonTI patients at week 24 crossed over to momelotinib, with 45.7% achieving TI at week 12. Besides, most adverse events were observed as grade 1-2 for both treatment groups within the 2 weeks after crossover from RUX to momelotinib. Finally, no RUX cytokine withdrawal symptoms were observed after the immediate RUX to momelotinib transition.
Momelotinib is an oral activin A receptor type 1 (ACVR1), JK1, and JK2 inhibitor that has shown promising results in preclinical and clinical translational studies. The inhibitor improves anemia and transfusion dependency through its differentiated suppression of ACVR1-mediated hepcidin production.
While most patients are at risk for decreased overall survival (OS) following discontinuation of RUX, momelotinib has potentially demonstrated that achieving week 24 TI response is associated with prolonged OS.
Mesa R, Verstovsek S, Platzbecker U, et al. Clinical outcomes of patients with myelofibrosis after the immediate transition to momelotinib from ruxolitinib. Haematologica. Published online June 1, 2023. doi:10.3324/haematol.2023.283106