Monitoring Ruxolitinib Responses Could Optimize Treatment for Polycythemia Vera
Key Takeaways:
- Among patients with polycythemia vera (PV), ruxolitinib treatment initiation was associated with reductions in leukocytosis, thrombocytosis, and phlebotomy requirements.
- Complete hematologic response (CHR) and spleen reduction emerged as predictors of improved survival outcomes.
- Based on these findings, researchers developed the PV Response to Ruxolitinib After 6 Months (PV-RR6), a prognostic model to help providers identify patients at increased risk of poor outcomes.
Ruxolitinib is a Janus kinase (JAK) inhibitor approved for the treatment of patients with PV who have an inadequate response to or are intolerant of hydroxyurea. Previous studies have demonstrated durable responses to ruxolitinib and a manageable safety profile. However, additional research is needed to identify prognostic factors that can predict long-term outcomes.
Researchers conducted a large, multicenter, real-world analysis to identify clinical factors associated with long-term outcomes and to develop a new prognostic model for patients with PV treated with ruxolitinib. The study included 178 patients who received ruxolitinib for at least 6 months between January 1985 and December 2023.
Outcomes included event-free survival (EFS) and myelofibrosis-free survival (MF-FS). Events evaluated included progression to post-PV MF, thrombosis, and hemorrhage.
Impact of Ruxolitinib on PV
Among the 178 patients, 57.9% were phlebotomy-free at treatment initiation. At the 3-month and 6-month follow-ups, the proportion of patients who were phlebotomy free increased to 87.1% and 90.4%, respectively. In addition, the proportions of patients without leukocytosis and thrombocytosis increased by 23.2% and 17.0%, respectively, at 6 months.
At 3 months, 22.5% of patients achieved CHR. The 5-year EFS rate was higher among patients who achieved CHR than among those who did not (82.6% vs 65.9%, respectively). CHR was also associated with higher MF-FS rates (90.2% vs 80.3%, respectively).
At baseline, 92 patients had splenomegaly. Of these, 46 achieved a spleen reduction of 50% or greater (SR50) at 3 months. At 6 months, 58 patients (63.0%) achieved SR50, including 21 (22.8%) who achieved both spleen and hematologic responses. Patients who achieved SR50 had higher EFS and MF-FS rates than those who did not (72.9% vs 46.8% and 83.3% vs 52.6%, respectively).
The PV-RR6 Model
Based on these findings, researchers developed the PV-RR6 prognostic model to identify patients at increased risk for poor health outcomes or adverse events. Patients are classified into 1 of 3 risk categories: low (score 0), intermediate (score 1-2.5), or high (score of 3 or greater).
The PV-RR6 model highlights the importance of dynamic risk monitoring in treatment decisions and dose optimization among patients with PV.
Implications for Managed Care
The findings highlight the clinical benefits observed with ruxolitinib among patients with hydroxyurea-resistant or hydroxyurea-intolerant PV and suggest that spleen response, CHR, and phlebotomy requirements may help predict long-term outcomes.
The authors said, “[L]ack of spleen response, absence of CHR, and especially persistent phlebotomy requirements should be regarded as clinically relevant warning signals, prompting consideration of dose optimization or treatment switch.”
Reference
Palandri F, Dedola A, Caocci D, et al. A dynamic prognostic model for polycythemia vera long-term outcomes in patients treated with ruxolitinib. Blood Adv. 2026;10(15):5469–5479. doi:10.1182/bloodadvances.2026020255
