Year in Review: Updates in Treating Myelofibrosis

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss how JAK inhibitors have reduced spleen size (splenomegaly) and constitutional symptoms like fatigue and fever in patients with myelofibrosis but that there is still room for improvement in treating other aspects of the disease like anemia and bone marrow fibrosis. They also share insights about the potential for combination therapies that target multiple pathways.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss how the combination of the BET inhibitor pelabresib and the JAK inhibitor ruxolitinib led to greater reductions in spleen size and symptoms compared to ruxolitinib alone in JAK inhibitor-naïve patients with intermediate- or high-risk myelofibrosis in the MANIFEST and MANIFEST-2 trials, with an acceptable safety profile, providing evidence that targeting multiple inflammatory pathways could lead to better disease control.

Andrew Kuykendall, MD, reviews data from TRANSFORM-1 on navitoclax plus ruxolitinib for untreated myelofibrosis, highlighting consistent response rates, no significant symptom improvement with the combination, and challenges managing thrombocytopenia caused by navitoclax, despite its activity and potential as a second-line treatment option.

Raajit K. Rampal, MD, PhD, discusses promising data on navtemadlin plus ruxolitinib for patients with myelofibrosis who had suboptimal responses to ruxolitinib, showing significant improvements in spleen and symptom responses, with further phase 3 studies anticipated.

Andrew Kuykendall, MD, highlights the potential of selinexor plus ruxolitinib in JAK inhibitor-naïve patients with MF based on promising response rates in XPORT-MF-034 updated results, with plans for a phase 3 study. He also noted the need to manage nausea as a adverse effect.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss luspatercept with or without ruxolitinib for the treatment of anemia in patients with myelofibrosis. The combination has demonstrated promise in reducing transfusion dependency, as seen in data from ACE-536-MF-001, with ongoing phase 3 trials.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, reflect on the future of combination therapies in treating myelofibrosis, emphasizing the need to align study endpoints with treatment goals and highlighting the potential of various combinations based on promising preclinical and early phase study results.

Drs Rampal and Kuykendall highlight the benefits of pacritinib for patients with low platelet counts, as evidenced by the PERSIST-2 study, and momelotinib for patients with anemia, as shown in the MOMENTUM Phase 3 Study, focusing on their efficacy in spleen volume reduction and symptom relief in patients with myelofibrosis.

Andrew Kuykendall, MD, discusses the efficacy and adverse effects of fedratinib, highlighting its potential in the second-line setting for patients resistant to ruxolitinib, with updates from FREEDOM-2 emphasizing manageable gastrointestinal tolerability concerns.

Raajit K. Rampal, MD, PhD, discusses choosing among JAK inhibitors based on specific patient needs, such as platelet counts and anemia, emphasizing the importance of using the full dose for best efficacy and how different scenarios might influence the choice and sequencing of these drugs in practice.

Andrew Kuykendall, MD, emphasizes the importance of individualizing therapy for patients with myelofibrosis, focusing on improving quality of life and addressing specific issues like anemia and spleen volume, with the understanding that these treatments are palliative and goals should be revisited regularly.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, conclude that the increasing complexity in myelofibrosis treatment options, including multiple JAK inhibitors and emerging combination therapies, signals an exciting era of individualized care, yet underscores the need for reevaluating study end points to enhance patient outcomes further.