JAK inhibition in myelofibrosis: how to sequence treatment in this new era of multiple options

The management of myelofibrosis has improved following approval of the JAK1/JAK2 inhibitor, ruxolitinib. This agent laid the foundation for JAK inhibitor therapy, yet limitations have included myelosuppression and other adverse events (skin cancer, weight gain, and infection), as well as loss of response. Recently, two additional JAK inhibitors were approved for use in myelofibrosis. Fedratinib can be used front-line and has demonstrated impressive responses as a salvage option after ruxolitinib loss of response. Previously, patients with severe thrombocytopenia had limited treatment options; approval of pacritinib offers an option to address splenomegaly and/or symptoms in these patients. A significant unmet need has been the treatment of anemia; momelotinib (not approved at the time of writing) has demonstrated spleen, symptom, and anemia responses. The possibility of having four approved options for myelofibrosis may be soon realized. This speaks to progress in the past decade, though achieving clinical and molecular remissions remain paramount.