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News
With four JAK inhibitors now approved for myelofibrosis, experts say maintaining dose intensity — not just picking a drug — is the key to better outcomes. Dr. Raajit Rampal of Memorial Sloan Kettering breaks down how cytopenia status should guide agent selection, and why emerging combinations and anemia-directed therapies could reshape the treatment landscape in the years ahead.
With four JAK inhibitors on the market for myelofibrosis — ruxolitinib, fedratinib, momelotinib, and pacritinib — the real challenge isn't just which drug to choose, but how to use it optimally. Dr. Raajit Rampal of Memorial Sloan Kettering emphasizes that maintaining dose intensity should be the guiding principle. For ruxolitinib, that means targeting 10 mg twice daily or higher when safe, even in patients with lower platelet counts. When that's not feasible, momelotinib (suited for anemia) and pacritinib (no dose reduction required regardless of platelet count) offer full-dose alternatives.
Beyond approved agents, combination strategies are generating buzz. Phase 3 data show that adding pelabresib or selinexor to ruxolitinib improves spleen volume responses — a clinically meaningful endpoint, especially for patients heading to stem cell transplant, where a smaller spleen means faster engraftment. CALR mutation–targeted therapies and anemia-directed agents like luspatercept and elritercept are also expanding the toolkit, with luspatercept already used off-label and embedded in NCCN guidelines.
Key Takeaways
Why it matters: As the myelofibrosis treatment landscape grows more complex, clinicians need a clearer framework for sequencing and combining therapies. The emerging data suggest that treating earlier and more aggressively — with the right agent at the right dose — could meaningfully improve survival and quality of life for patients.
