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SOHO 2026 | Exploring JAK inhibitor-based combination strategies in myelofibrosis

Naveen Pemmaraju, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the ongoing debate around combination therapy for patients with myeloproliferative neoplasms (MPNs), particularly intermediate- to high-risk myelofibrosis. Dr Pemmaraju outlines three JAK inhibitor-based strategies under investigation: frontline combination therapy, add-on therapy for suboptimal responders, and novel combinations following JAK inhibitor resistance or intolerance. This interview took place at the 14th Annual Meeting of the Society of Hematologic Oncology (SOHO 2026) in Houston, TX.

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Transcript

An excellent question about combination therapy in treating patients with intermediate to high-risk MF. So again, building on the concepts here at SOHO, I should emphasize that a standard of care, the only approved therapies are the fiyr monotherapy JAK inhibitors. So ruxolitinib, fedratinib, and pacritinib and momelotinib for their specific on-label indications. So that means that our field is still standard of care, JAK inhibitor monotherapy, and then you need to make a decision with your patient, stem cell transplant or not, and then base your curative approach on that...

An excellent question about combination therapy in treating patients with intermediate to high-risk MF. So again, building on the concepts here at SOHO, I should emphasize that a standard of care, the only approved therapies are the fiyr monotherapy JAK inhibitors. So ruxolitinib, fedratinib, and pacritinib and momelotinib for their specific on-label indications. So that means that our field is still standard of care, JAK inhibitor monotherapy, and then you need to make a decision with your patient, stem cell transplant or not, and then base your curative approach on that. So now as we go into the investigational approach, as I mentioned before, there are multiple clinical trials ongoing, and they fall into, interestingly, three buckets. And it’s important to think about it. Number one is adding in the novel combination agent upfront. So that’s frontline combination. The goal there may be a bit more increased toxicity, perhaps, but trying to get a better induction phase where perhaps you get a better, deeper, stronger, more durable spleen volume response and then decide transplant or not. Number two is the so-called add-on approach, suboptimal. You’re on the JAK inhibitor. We believe that about three to six months of the JAK inhibitor is where you’re going to see your maximum response. And then if you’re still not getting the spleen or symptom benefit that you want for your patient, can you now add in the second agent? And then third is patient has become intolerant or the JAK inhibitor is not working at all. Now we discontinue that and then we go to a novel approach after that. So I would say these are all in investigational clinical trials. None of these are yet FDA-approved. And so I would refer folks to clinicaltrials.gov and our ongoing clinical trials at our centers to see which ones might be appropriate for the right patients.

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