New Drugs in Myelofibrosis: Incremental Progress in Symptom Management Without Disease Modification.
Key claim: In myelofibrosis, ruxolitinib combinations and emerging CALR- and anemia-directed agents improve spleen and symptom control with limited disease modification, so strategies should prioritize transplant and survival endpoints.
Abstract
Janus kinase inhibitors are the cornerstone of treatment for myelofibrosis, but have limited disease-modifying activity. Combinations of ruxolitinib with pelabresib, navitoclax, or selinexor improve spleen responses, although benefits for symptoms and anemia are less consistent, and toxicity may increase. Such approaches may optimize splenomegaly before transplantation. Emerging CALR-directed therapies, particularly INCA033989, offer potential for selective suppression of the malignant clone while improving spleen, anemia, and symptom outcomes. Anemia-directed agents targeting TGF-β/BMP-SMAD signaling, including luspatercept, elritercept, and selcodebart, may reduce transfusion burden. Future strategies should align treatment with therapeutic intent and prioritize transplantation, molecular response, progression-free survival, and overall survival endpoints.
Why this matters
In myelofibrosis, ruxolitinib combinations and emerging CALR- and anemia-directed agents improve spleen and symptom control with limited disease modification, so strategies should prioritize transplant and survival endpoints.