Mitigating Potential Treatment Risks Among Patients With Myelofibrosis

Aaron Gerds, MD, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, examines potential treatment risks for myelofibrosis, including peripheral neuropathies, myelosuppression, and anemia, and discusses how to mitigate them in order to achieve the best possible outcomes.

Transcript: 

Dr Gerds: My name is Aaron Gerds, and I'm the lead author of a paper that was published in Lancet Hematology regarding the MOMENTUM Study, a prospective randomized trial with momelotinib versus danazol in patients with myelofibrosis. I'm currently an associate professor of medicine at the Cleveland Clinic Taussig Cancer Institute. 

Oncology Learning Network: Do you have any specific concerns about the treatment of myelofibrosis? If so, how do you mitigate these setbacks or risks in treatment?

Dr Gerds: Early on in the development of momelotinib, there was a concern over an increased risk of peripheral neuropathies. However, in the large randomized phase 3 trials, the rates of peripheral neuropathy were quite low: all less than 5% in the study population. In fact, in the MOMENTUM study it was 2 to 3%, and more importantly, comparing momelotinib to danazol, there were equal rates of peripheral neuropathy seen. So, that concern, I think, is a little less, although we should still continue to be observant of signs and symptoms of peripheral neuropathy in patients with myelofibrosis in general. 

There were also some instances of myelosuppression seen with momelotinib, namely lowering of the platelet counts. Then, some patients also did develop anemia, even though it is a drug designed in part to alleviate anemia. So, monitoring blood is an important part of taking care of these patients going forward.

The other side effects that emerged as relatively more common were [gastrointestinal] (GI) side effects—mild nausea and diarrhea—that may require the use of an antiemetic or anti-diarrheal, particularly within the first 1 to 2 months of treatment. Unlike ruxolitinib, there was no increase [in] weight observed, or increase in cholesterol levels observed. Unlike fedratinib, there were no observed cases of wares, Wernicke's encephalopathy, and unlike pacritinib, there was no evidence of QTc prolongation. Those specific monitoring patterns for those other [Janus kinase] (JAK) inhibitors may not be necessary for momelotinib, albeit we want to keep these things mindful because some of these effects may be a class effect.

Source: 

Gerds AT, Verstovsek S, Vannucchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. Lancet Haematol. Published online: September 2023. doi:10.1016/S2352-3026(23)00174-6