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).

Ayalew Tefferi, M.D.

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.

Kelley Luedke

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.