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ESH CML/MPN 2025 | Combination therapy in myelofibrosis: reviewing the data and testing new combinations
Michael Loschi, MD, PhD, University Hospital of Nice, Nice, France, provides insight into a satellite symposium on combination therapy in myelofibrosis (MF), highlighting data from trials combining ruxolitinib with pelabresib and ruxolitinib with navitoclax. Despite these combinations resulting in a minimum reduction of 35% in spleen volume (SVR35), Dr Loschi notes that fatigue remains a significant challenge. The combination of selinexor and ruxolitinib, which is being explored in the Phase III XPORT-MF-034 study (NCT04562389), may improve this symptom in patients. This interview took place at the European School of Haematology (ESH) 4th How to Diagnose and Treat: CML/MPN meeting in Vienna, Austria.
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Transcript
We had the opportunity with Professor Passamonti and Dr O’Sullivan to first review the results of combos in first-line therapy for myelofibrosis patients, chronic-phase myelofibrosis patients, and especially saw the MANIFEST-2 trial combining RUX and pelabresib that reached its primary endpoint of the SVR35, but unfortunately didn’t reach the TSS50 endpoint...
We had the opportunity with Professor Passamonti and Dr O’Sullivan to first review the results of combos in first-line therapy for myelofibrosis patients, chronic-phase myelofibrosis patients, and especially saw the MANIFEST-2 trial combining RUX and pelabresib that reached its primary endpoint of the SVR35, but unfortunately didn’t reach the TSS50 endpoint.
And we also reviewed the data of the TRANSFORM trials of the combination of RUX plus navitoclax versus RUX plus placebo as a first-line treatment for patients with chronic phase myelofibrosis. And for this trial, too, the primary endpoint was achieved, but not the TSS50 secondary endpoint.
So pretty good results of these two combinations on the disease burden, on several biological parameters, myelofibrosis, cytokines, marrow environment, erythropoiesis, but unfortunately, it remains the problem of the symptoms and especially the fatigue that’s not improved by the combination. We underline the fact that fatigue is pretty hard to improve, even in the general population. So probably the criteria of the trials leading to new drug approval in myelofibrosis should probably be modified.
Yeah, so basically, this was the first part of the meeting, and then I had the opportunity to present a new combo that’s an association between selinexor and ruxolitinib that has first been studied in a Phase I trial comparing two different dosages of selinexor, one of 40 milligrams once a week, and the other one, 60 milligrams once a week with very interesting results in this Phase I study, with all patients achieving the SVR35, all patients achieving an improvement of the TSS with all patients reaching TSS50. And so this Phase I led to the actual XPORT-MF-034 trial, which is a phase three double-blind randomized international trial comparing as a first-line trial for chronic phase myelofibrosis patients the combo ruxolitinib plus selinexor versus ruxolitinib alone plus placebo.
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Disclosures
Honoraria: Stemline.
