Survival and Response Outcomes in Myelofibrosis Patients Treated with Four JAK2 Inhibitors

Overview

This retrospective study compared long-term outcomes of 183 myelofibrosis patients treated with momelotinib, ruxolitinib, fedratinib, or BMS-911543. Momelotinib-treated patients, despite higher baseline risk and transfusion dependence, showed longer treatment duration and favorable anemia response. Treatment response and molecular risk factors influenced overall and leukemia-free survival.

Background

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, and anemia. JAK2 inhibitors (JAKi) such as ruxolitinib, fedratinib, and pacritinib are FDA-approved for MF, providing symptom relief and spleen size reduction but differ in anemia management. Momelotinib is a promising JAKi with notable anemia benefits awaiting FDA approval. Understanding how these therapies impact long-term survival and response predictors is critical for optimizing MF management.

Data Highlights

Key Findings

• Momelotinib-treated patients were older, more transfusion-dependent, and had higher DIPSS-plus high-risk status but experienced longer median treatment duration (21 months) compared to ruxolitinib (10 months).
• Spleen and symptom response rates were comparable between momelotinib and ruxolitinib, but momelotinib showed superior anemia response.
• Overall, 97% of patients discontinued therapy by median 3.7 years, with suboptimal response or progression being the most common reason (61%).
• Mutation profiles were similar across treatment groups, with JAK2 mutations in 80% and ASXL1 mutations in 47% of evaluable patients.
• Patients on fedratinib had higher leukocytosis and thrombocytosis, while BMS-911543 patients were more often female and had more constitutional symptoms.

Clinical Implications

Momelotinib may offer advantages in managing anemia and sustaining longer treatment duration in higher-risk MF patients compared to other JAK2 inhibitors. Clinicians should consider baseline patient characteristics, including transfusion dependence and risk stratification, when selecting JAKi therapy. Monitoring for treatment discontinuation reasons, especially suboptimal response, remains essential for optimizing patient outcomes.

Conclusion

This study highlights differential patient characteristics and treatment outcomes among JAK2 inhibitors in MF, with momelotinib showing promising anemia benefits and longer therapy duration despite higher baseline risk. These findings support individualized therapy selection and further investigation into survival impacts of JAKi responses.

References

1. Tefferi et al. 2023 -- Factors Influencing Survival and Comparative Analysis of 183 Patients with Myelofibrosis Treated with Momelotinib, Ruxolitinib, Fedratinib, or BMS-911543 JAK2 Inhibitor