For myelofibrosis, JAK inhibitors remain the therapeutic backbone, and the field now has four approved agents, each suited to a different clinical problem. Ruxolitinib and fedratinib reduce spleen size and symptoms but are myelosuppressive; pacritinib is chosen for patients with significant thrombocytopenia (platelets below 50); and momelotinib — which the earlier literature listed as investigational but which was approved in 2023 — is valuable for patients with anemia, achieving transfusion independence in some (the MOMENTUM trial). A key limitation is that none of these clearly modifies the disease course or prolongs survival; they are symptom- and spleen-directed.
The most active research effort is combination therapy built on a ruxolitinib backbone, aiming for deeper, potentially disease-modifying responses: the BET inhibitor pelabresib (MANIFEST-2), the BCL-xL inhibitor navitoclax (TRANSFORM-1), and agents such as selinexor are in late-stage trials, though none has yet displaced JAK-inhibitor monotherapy as standard. Immune-based and novel targeted approaches are also emerging across the myeloproliferative neoplasms.
Further reading: JAK-inhibitor sequencing in myelofibrosis (Masarova & Chifotides, Blood 2025); momelotinib MOMENTUM and 2023 approval; myelofibrosis emerging treatments (Harrison et al., 2024).