Harrison CN, et al. - In this study, the efficacy and safety of momelotinib, a Janus kinase (JAK) 1 and JAK 2 inhibitor, vs best available therapy (BAT) were assessed in patients with myelofibrosis who had suboptimal responses or haematological toxic effects with ruxolitinib. Momelotinib proved not to be superior to BAT for the reduction of spleen size by at least 35% compared with baseline in patients with myelofibrosis previously treated with ruxolitinib.

Methods

• Researchers performed a randomised, phase 3, open-label trial; patients were screened for eligibility from 52 clinical centres in Canada, France, Germany, Israel, Italy, Spain, the UK, and the USA.
• This study included patients who had myelofibrosis and previous ruxolitinib treatment for at least 28 days who either required red blood cell transfusions while on ruxolitinib or ruxolitinib dose reduction to less than 20 mg twice a day with at least one of grade 3 thrombocytopenia, anaemia, or bleeding at grade 3 or worse, with palpable spleen of at least 5 cm and without grade 2 or greater peripheral neuropathy.
• Random assignment of patients (2:1) to either 24 weeks of open-label momelotinib 200 mg once a day or BAT (which could include ruxolitinib, chemotherapy, steroids, no treatment, or other standard interventions) was performed, after which all patients could receive extended momelotinib treatment.
• They randomly assigned patients to treatment by an interactive web response system and stratified the randomisation by transfusion dependence and by baseline total symptom score (TSS).
• On an intention-to-treat basis, results were analysed.
• A reduction by at least 35% in the spleen volume at 24 weeks compared with baseline was observed as the primary endpoint.
• Adverse event monitoring was included in safety analyses.

Results

• Researchers recruited 156 patients in this study, from June 19, 2014 to July 28, 2016; 104 received momelotinib and 52 received BAT.
• In 46 (89%) of 52 patients, BAT was ruxolitinib.
• The 24-week treatment phase was completed by 73 (70%) of 104 patients in the momelotinib group and 40 (77%) of 52 patients in the BAT group.
• A reduction in the spleen volume by at least 35% compared with baseline was evident in 7 (7%) of 104 patients in the momelotinib group and 3 (6%) of 52 in the BAT group (proportion difference [Cochran–Mantel–Haenszel method], 0·01; 95% CI -0·09 to 0·10), p=0·90).
• Anaemia (14 [14%] of 104 in the momelotinib group vs seven [14%] of 52 in the BAT group), thrombocytopenia (seven [7%] vs three [6%]), and abdominal pain (one [1%] vs three [6%]) were identified as the most common grade 3 or worse adverse events.
• Eleven (11%) of 104 patients receiving momelotinib (one of which was grade 3) and no patients in the BAT group experienced peripheral neuropathy. .
• Thirty-six (35%) patients in the momelotinib group and 12 (23%) of patients in the BAT group experienced serious events.
• Due to adverse events, deaths were reported for 6 patients (6%) receiving momelotinib (acute myeloid leukaemia [n=2], respiratory failure [n=2, with one considered possibly related to momelotinib], cardiac arrest [n=1, considered possibly related to momelotinib], and bacterial sepsis [n=1]); and 4 patients (8%) receiving BAT (lung adenocarcinoma [n=1], myelofibrosis [n=1], and sepsis [n=2]).