What are the therapeutic options for previously treated myelofibrosis?

Introduction: The disruption of the JAK/STAT signaling pathway is a defining feature of myelofibrosis (MF). The introduction of JAK inhibitors (JAKi) has transformed the therapeutic approach to MF, becoming essential to treatment and reshaping the management landscape. While JAKi are now the preferred first-line treatment for most patients, various management options are available for those who do not respond to initial therapy.

Areas covered: This review focuses on management options for patients with MF, with particular emphasis on therapeutic strategies following the failure of first-line JAKi. It provides a comprehensive overview of the current treatment landscape, including alternative JAKi and other approaches. The review is based on an extensive literature search using available databases (PubMed, Cochrane …) and relevant web resources (clinicaltrials.gov).

Expert opinion: Ruxolitinib benefits in MF often diminish after 3-4 years, with complications like thrombocytopenia and anemia. Three newer JAKi offer alternatives with similar efficacy and varied side effects. Stem cell transplantation is a curative option for a minority, ideally timed at peak response to JAKi. Research aims to enhance first-line treatments and restore responses in resistant patients. Future therapies may include novel combinations or immunotherapies targeting specific mutations, requiring collaboration between patient, clinical, and pharmaceutical communities.