Navigating Adverse Effects of JAK Inhibitors in Myeloproliferative Neoplasms

Prithviraj Bose, MD, professor in the Department of Leukemia at MD Anderson Cancer Center, discusses the most critical adverse effects (AEs) seen with each of the 4 approved JAK inhibitors for the treatment of myeloproliferative neoplasms.

He continues by explaining how the AEs observed typically are managed in these patients.

Transcription:

0:09 | The 4 approved drugs have different [adverse] effects. Ruxolitinib [Jakafi] is most known for the cytopenias that it causes, and same with fedratinib [Inrebic]. For both of them, anemia, thrombocytopenia, are big. Now we can dose-adjust, try and support the anemia with other agents like danazol, luspatercept [Reblozyl], erythropoiesis-stimulating agents, but then we have to think about some unique [adverse] effects for each drug which are not necessarily hematologic.

0:55 | With ruxolitinib, weight gain can be a problem in some patients. Shingles and basal and squamous cell skin cancer risk can be significant, especially in [patients] who have had these before. I give the shingles vaccine to every patient that gets ruxolitinib.

1:20 | With fedratinib and pacritinib [Vonjo], [there are] a lot of [gastrointestinal adverse] effects like nausea, vomiting, and diarrhea. Diarrhea [and nausea are seen more] with pacritinib than fedratinib, but thankfully, mostly early on. We manage these with antiemetics and antidiarrheals, and one has to be proactive about that. I will be remiss not to mention that fedratinib has a black box warning about Wernicke encephalopathy, which is super rare, fortunately, but something that we want to prevent by giving thiamine supplementation and also by checking thiamine levels.

2:04 | Finally, momelotinib [Ojjaara], again, the most recent, can cause thrombocytopenia. That is not trivial. It certainly occurs in about a quarter of the patients. Diarrhea, too, occurs in about a quarter of the patients. Then [there is] some rare stuff, like infections, peripheral neuropathy, but those are fortunately uncommon. There is one unique thing about momelotinib, which is that it can cause this first-dose hypotension. [Patients] are well advised to take it at bedtime, especially towards the beginning.