Novel therapies vs hematopoietic cell transplantation in myelofibrosis: who, when, how?

Abstract

Abstract Myelofibrosis is one of the classical Philadelphia chromosome–negative myeloproliferative neoplasms characterized by progressive marrow failure and chronic inflammation. Discovery of the JAK2 mutation paved the way for development of small molecular inhibitors and further facilitated the research in understanding of molecular biology of the disease. Development of novel medications and synergistic combinations with standard JAK inhibitor (JAKi) therapy may have the potential to improve depth and duration of disease control and symptomatic benefit, whereas advancements in allogeneic hematopoietic stem cell transplantation (HCT) have improved tolerability and donor availability, allowing for more patients to pursue this potentially curative therapy. The increase in options for medical therapy and changing risk profile of HCT is leading to increased complexity in counseling patients on choice of management strategy. In this case-based review, we summarize our approach to symptom-directed medical therapy, including the use of novel drugs and combination therapies currently under study in advanced clinical trials. We outline our recommendations for optimal timing of HCT, including risk-adapted selection for early HCT as opposed to delayed HCT after upfront JAKi therapy, as well as the use of pretransplant JAKi and alternative donor sources.