Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.

Somatic mutations (for example, CALR, ASXL1) and karyotype have been shown to independently influence survival in patients with myelofibrosis (MF).1, 2 The objectives of the current study were to determine if such genetic markers also influence treatment response in MF patients receiving single agent momelotinib and whether such therapy overcomes the detrimental effect of prognostically relevant mutations in MF. Momelotinib is a Janus kinase (JAK)-1/2 inhibitor currently being evaluated in phase-3MF clinical trials (NCT01969838, NCT02101268). In an earlier phase-1/2 study (n=166), the drug was shown to improve anemia (53% response rate), reduce spleen size (39% response rate) and alleviate constitutional symptoms (>50% response rate) in MF patients.3 The current study considers 100 consecutive patients, who were part of the aforementioned phase-1/2 study and received momelotinib therapy at the Mayo Clinic.