Managing and Understanding Toxicities Associated With Myelofibrosis Therapy

CancerNetwork® spoke with Prithviraj Bose, MD at the Society of Hematologic Oncology 2025 Annual Meeting following a presentation he delivered titled “Individualizing Treatment Selection for [myelofibrosis]”.

During the discussion, he considered the toxicities that different myelofibrosis treatments may elicit. With ruxolitinib (Jakafi), an FDA-approved JAKinhibitor, anemia, thrombocytopenia, weight gain, shingles, and non-melanoma skin cancer are all adverse events that patients may experience. Fedratinib (Inrebic), another FDA-approved JAKinhibitor, may lead to gastrointestinal toxicity; there is also the possibility of Wernicke’s encephalopathy. Pacritinib (Vonjo), another therapy, may lead to gastrointestinal toxicity and diarrhea, as well as bleeding and cardiovascular events. Momelotinib (Ojjaara), the last of the FDA-approved JAKinhibitors, may lead to thrombocytopenia, diarrhea, and, rarely, peripheral neuropathy and liver function alterations.

Bose is a professor in the Department of Leukemia in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center.

Transcript:

Toxicities are important. We have to consider each of our 4 drugs. For ruxolitinib, anemia is the biggest issue, [along with] thrombocytopenia. Beyond that, weight gain, shingles, and non-melanoma skin cancer have to be kept in mind because these can accumulate over time and become a problem.

With fedratinib—I will just go in order of approval—you have to think about [gastrointestinal] toxicity, particularly in the first cycle. You have to manage that proactively. All patients on fedratinib should receive thymine supplementation. There is a black box warning about Wernicke’s encephalopathy, so thiamine becomes important. It is easy to do, cheap, and should prevent that problem.

With pacritinib, [there is gastrointestinal] toxicity and diarrhea in the first 8 weeks; that has to be dealt with in a proactive fashion, but it can also cause bleeding and cardiovascular events. One has to be a little bit careful about patient selection and not have blood thinners or QT-prolonging drugs on board, et cetera.

Momelotinib is the latest to be approved 2 years ago. That’s the one that brings the greatest anemia benefit. We’ve touched on that already in the context of ruxolitinib and the anemia that it causes, but momelotinib has some [adverse] effects. It can cause thrombocytopenia and diarrhea, which are generally manageable and not too big a deal. But then you can also, in rare cases, have peripheral neuropathy and some liver function alterations….It’s perhaps more fair to say “early” rather than just with the first dose…but hypotension and dizziness [can occur], which can affect patients, and they need to be warned about them.

Reference

Bose P. Individualizing treatment selection for MF. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, TX.