Assessing Genetic Determinants in Momelotinib-Treated Patients with Myelofibrosis
Somatic mutations, such as CALR and ASXL1, and karyotype have been shown to independently influence survival in patients with myelofibrosis (MF).
Mayo Clinic researchers, first author Ayalew Tefferi, M.D., conducted a study to determine if such genetic markers also influence treatment response in MF patients receiving single agent momelotinib and whether it overcomes the detrimental effect of prognostically relevant mutations in MF. The study was published in the journal Leukemia.
The study consists of 100 patients who were part of an earlier study that showed momelotinib therapy, a Janus kinase (JAK)-1/2 inhibitor, improved anemia, reduced spleen size, and alleviated constitutional symptoms in MF patients.
According to the results, patient survival was consistent with recent reports in the general population of patients with MF. Momelotinib treatment was unable to overcome the negative prognostic impact of mutational status in MF. This was also the case with ruxolitinib, another JAK-1/2 inhibitor. However, ruxolitinib-induced spleen response, which predated the discovery of CALR mutations, was reported to be independent of mutational status.
Based on these results, confirmation is required from the ongoing larger phase-3 studies of momelotinib therapy in MF. Similarly, it remains to be seen whether these observations can be generalized to other JAK inhibitors.