Myelofibrosis (MF)-associated
anemia and transfusion dependency are associated with inferior quality of life and poor prognosis. JAK2 inhibitors and TGF-β superfamily
ligand traps are being explored as treatment options for MF-associated
anemia. Here, we present the case of a 66-year-old man with heavily pretreated intermediate-2 (INT-2) risk primary MF who had an exceptional response to combination
fedratinib and
luspatercept therapy. He achieved transfusion independence and experienced a reduction in spleen size from 20 cm to 12 cm, with remarkable improvement in performance status. Compared with other
JAK inhibitors, the mechanism of action of
fedratinib may explain its milder effect on
anemia. It is possible that the addition of
luspatercept may result in an additive or synergistic effect of one or both medications. Although the exact
biological pathways have not yet been elucidated, combination
fedratinib and
luspatercept nevertheless is a promising
therapy for
anemia in patients with transfusion-dependent INT-2 risk MF.