- Vikas Gupta1,*,
- Ruben A. Mesa2,
- Michael W.N. Deininger3,
- Candido E. Rivera4,
- Shireen Sirhan5,
- Carrie Baker Brachmann6,
- Helen Collins6,
- Jun Kawashima6,
- Yan Xin6 and
- Srdan Verstovsek7
- 1 Princess Margaret Cancer Centre, University of Toronto;
- 2 Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ;
- 3 Division of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute;
- 4 Division of Hematology/Oncology, Mayo Clinic Jacksonville;
- 5 Division of Hematology, Jewish General Hospital;
- 6 Gilead Sciences, Inc.;
- 7 University of Texas MD Anderson Cancer Center
- ↵* Corresponding author; email:
Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, nonrandomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. Response assessment according to 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. Symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. This trial was registered at www.clinicaltrials.gov as NCT01423058.
- Received May 27, 2016.
- Accepted September 14, 2016.
- Copyright © 2016, Ferrata Storti Foundation