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EHA 2025 | An indirect comparison of the safety profiles of JAK inhibitors in patients with myelofibrosis
Lucia Masarova, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses an indirect treatment comparison between momelotinib and fedratinib or pacritinib, which assessed the safety profiles of these JAK inhibitors. The comparison highlighted that momelotinib had a more favorable side effect profile than the other agents, with a lower incidence of hematologic and gastrointestinal adverse events. This information may provide clinicians with more guidance on choosing between these agents in clinical practice. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
So the indirect matched comparisons of these agents of like the other JAK inhibitors will be probably the only way for us to see some kind of head-to-head comparisons although it’s very indirect and it’s matched so there’s no head-to-head comparisons of these agents. The only direct head-to-head in frontline patients with myelofibrosis was the SIMPLIFY-1, momelotinib versus ruxolitinib...
So the indirect matched comparisons of these agents of like the other JAK inhibitors will be probably the only way for us to see some kind of head-to-head comparisons although it’s very indirect and it’s matched so there’s no head-to-head comparisons of these agents. The only direct head-to-head in frontline patients with myelofibrosis was the SIMPLIFY-1, momelotinib versus ruxolitinib. So now onwards, because now we have four JAK inhibitors available, probably this is going to be all we’re going to see how these drugs compare to each other.
And in the MAIC, which is the indirect matched comparisons, was momelotinib data from all available randomized studies, and then either one study for pacritinib and the other for fedratinib, which are all excellent JAK inhibitors approved for patients with myelofibrosis, they’re just phased in a different level of the disease or how they’re given. So, momelotinib is an agent-approved for anemia. Pacritinib is a great agent-approved for patients with severe thrombocytopenia. And then, fedratinib, none of them has any other lines, so they could be used front-line or secondary. And fedratinib is an agent, basically, that has the strongest JAK2 inhibitions used for patients with large spleens or symptoms, mostly picked as a second-line setting because of side-effect profile.
And this comparison particularly looked at the side effect profile. And actually, after matching this patient from the studies for baseline characteristics, they were pretty broadly done. And while still the estimated sample size remained quite reasonable, the comparison showed that momelotinib had favorable profile for the incidence of most important adverse events, particularly hematologic, which we know for fedratinib, it’s an immunosuppressive drug, more than momelotinib or pacritinib, because all the other two are approved in a cytopenic setting. And then mostly for gastrointestinal, such as a grade, overall grade or grade 3, nausea, vomiting, diarrhea, where momelotinib shows superiority for actually against both of these agents. So separately for pacritinib patients as well as fedratinib patients.
So I would just say that this just gives us a little bit more room into how to phase and choose these drug inhibitors. I mean, in my opinion, all of them are necessary. We need more drugs for our patients. They all have different approvals. They all have a different setting and usage, but just be more conscious for what the side effect profiles of these agents offer. And particularly for drugs that offer or give more gastrointestinal toxicity, use preventive measures to avoid it, so patients could tolerate the drugs and remain on the medications for the longest benefit.
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