AI Summary
The article discusses the current unmet needs in the treatment of myelofibrosis (MF), a type of bone marrow disorder. The standard treatment options, such as inhibitors of the JAK/STAT pathway and stem cell transplantation, have limitations in terms of modifying the underlying disease and providing substantial survival benefits. The authors highlight the importance of developing safe and impactful therapies for lower risk patients, improving first-line treatments for intermediate/higher risk patients, and managing cytopenia. They also stress the necessity of defining disease modification in a consensus manner to inform trial design and develop more effective and safe treatment strategies for MF patients. Collaboration between clinicians, patients, and the pharmaceutical industry is essential in achieving these goals and improving the quality of life for individuals with MF.
Abstract
The current standard-of-care for treatment of myelofibrosis (MF) comprises inhibitors of the Janus kinase (JAK)/signal transducers and activators (STAT) pathway; however, despite their ability to alleviate symptoms, they do not appear to modify underlying disease and have not demonstrated substantial survival benefit. Allogeneic-hematopoietic stem cell transplantation remains the only curative option for patients with MF but is limited to a subset of high-risk and fit patients. Early disease modification could positively affect disease trajectory for lower risk patients with MF as well as those with conditions that can precede MF, such as polycythemia vera and essential thrombocythemia. Here, the authors discuss critical unmet needs in the MF treatment paradigm, including: the need for safe, impactful therapies for lower risk patients, thus allowing intervention when success is most likely; better development of first-line therapies (likely highly novel or combination strategies) for intermediate-risk/higher risk patients; and approved drugs to manage cytopenia. Finally, a consensus definition of disease modification is needed that informs trial design, allowing the development of clinical end points that enable understanding of therapies and responses and that facilitate the development of therapies that work according to this definition. Through close collaboration between clinicians, patients, and the pharmaceutical industry, better efforts to define benefit and identify patients most likely to benefit from a particular combination or treatment strategy should enable the development of more effective and safe treatments to extend and improve quality of life for patients with MF.