The 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO) delivered compelling evidence for the evolving treatment landscape of myelofibrosis, showcasing novel therapeutic approaches that address key unmet needs in this challenging bone marrow disorder. Researchers presented data on emerging JAK inhibitors and refined treatment strategies that promise to improve outcomes for patients struggling with this incurable condition.
Novel JAK Inhibitors Expand Treatment Options
Momelotinib Addresses Anemia Challenge
Momelotinib, an adenosine triphosphate-competitive JAK inhibitor targeting JAK1, JAK2, JAK3, and TYK2, has emerged as a significant advancement for patients with myelofibrosis-associated anemia. The drug received FDA approval in 2023 for treating patients with anemia and high/intermediate-risk myelofibrosis.
"Momelotinib was non-inferior in terms of spleen response. However, it was not non-inferior in terms of symptom improvement, where we saw ruxolitinib was associated with a symptom response or a 50% reduction in symptom score of 42% compared to just 28% with momelotinib," explained Dr. Andrew Tucker Kuykendall from H. Lee Moffitt Cancer Center and Research Institute.
The pivotal MOMENTUM trial demonstrated momelotinib's clinical advantage in a phase 3 study of patients with prior ruxolitinib exposure and anemia. Patients randomized 2:1 to receive momelotinib versus danazol showed a 25% symptom response rate compared to just 9% with danazol, and a spleen volume response rate of 22% versus 3%, respectively. Importantly, momelotinib was associated with improved rates of transfusion independence, addressing a critical unmet need in this patient population.
Pacritinib Offers Hope for Cytopenic Patients
Pacritinib, approved by the FDA in 2022 for treating primary and secondary myelofibrosis in patients with platelet counts less than 50 x 10⁹/L, targets JAK2 and FMS-like tyrosine kinase 3. The drug demonstrated clinical benefit in the PERSIST-1 and PERSIST-2 studies, particularly in patients with cytopenias.
"The responses observed with pacritinib do not appear to be affected by baseline cytopenias. The rates of achieving a spleen volume reduction of 35% and greater or symptom improvement of 30% to 50% are comparable regardless of whether a patient's hemoglobin is above 10 g/dL, between 8 to 10 g/dL, or whether they have low platelet counts," noted researchers.
PERSIST-1 met its primary endpoint, demonstrating a spleen volume response rate of 19% compared with 5% with standard treatment in frontline patients with higher-risk myelofibrosis. A post-hoc analysis revealed that pacritinib is also a potent ACVR1 inhibitor, which may contribute to its potential anemia benefits.
Ruxolitinib Remains Treatment Cornerstone
Despite emerging alternatives, ruxolitinib continues as the standard of care for myelofibrosis treatment. "JAK inhibitors are the mainstay of treatment for myelofibrosis," said Dr. Kuykendall. "We'd certainly like to change that and bring new agents to the table, but it remains the JAK inhibitors are the common, most common therapy for our patients."
Approved by the FDA in 2011, ruxolitinib provides substantial clinical benefits including reducing spleen volume by over 35%, rapid improvements in disease-related symptoms, and potential survival benefit, especially in early disease stages. However, the drug is strongly associated with dose-dependent anemia development or worsening of existing anemia.
Pegylated Interferons Show Enduring Value
Pegylated interferons continue to demonstrate relevance in myelofibrosis treatment, particularly for younger patients. "Interferons are absolutely still a major player in MPNs. They have high clinical efficacy and manageable toxicities, superior molecular responses, and potential disease-modifying activity," researchers emphasized.
These agents have shown high clinical efficacy in patients with essential thrombocythemia and polycythemia vera, with response rates around 80%. Phase 2 studies have consistently reported response rates of 70% to 80%. In the PROUD-PV study, sustained responses were observed at 36 months, with a 71% response rate in patients treated with ropeginterferon compared to 51% in those receiving hydroxyurea.
Personalized Treatment Approaches
The conference emphasized the importance of personalized treatment plans tailored to individual patient needs based on genetic markers and disease severity. Presentations focused on investigational drugs designed to address underlying genetic mutations associated with myelofibrosis, as well as treatments aimed at reducing spleen size and alleviating anemia—two common complications of the disease.
Experts noted that these developments represent significant progress in understanding myelofibrosis and its impact on patients' quality of life. The findings presented at ASCO 2025 are expected to contribute to shaping future research efforts and clinical guidelines for managing this complex condition.
As research in myeloproliferative neoplasms continues to evolve, the treatment landscape for myelofibrosis is expanding beyond traditional approaches. Although JAK inhibitors like ruxolitinib remain foundational in clinical practice, novel agents such as momelotinib and pacritinib offer meaningful advantages for patients with anemia or thrombocytopenia. Together, these emerging and established therapies pave the way for a broader movement toward more personalized, tolerable, and disease-modifying strategies.
