Optimal Ruxolitinib Dosing in Myelofibrosis Critical for Improved Effectiveness, Survival in Real-World Setting

Patients with myelofibrosis (MF) started on appropriate and highest tolerated doses of ruxolitinib (Jakafii; Incyte Corporation) experienced better trends in response and improved health-related quality of life (HRQoL), highlighting the importance of proper ruxolitinib dosing, timing, and administration to ensure the most effective patient responses in terms of symptom relief, spleen size reduction, and improved overall survival (OS).¹

Ruxolitinib is effective at reducing symptoms in myelofibrosis. | Image Credit: © shidlovski - stock.adobe.com

It's critical for treatment providers administering ruxolitinib for MF to know the expected real-world presentation of treatment complications. Patients being administered ruxolitinib face higher health care resource utilization and clinical burdens, including an increased risk of anemia development and adverse treatment events. Still, the treatment is highly effective when dosed and administered appropriately and when proper consideration of adverse events, such as anemia or graft-versus-host disease, is included in counseling.^1,2

According to the investigators, the expected optimal starting dose for initiating ruxolitinib is based on a patient’s baseline platelet count. Further dose titration—up to 25 mg twice daily—can be utilized to maximize efficacy, which has been demonstrated to be dose-dependent. However, suboptimal adherence is consistently reported among patients treated with ruxolitinib, which could contribute to poor survival outcomes and undermine disease control.^1,3

Poor adherence rates have been observed in the ongoing Ruxolitinib Observational Study in Myelofibrosis Treated Patients in Italy (ROMEI), an observational study of ruxolitinib-treated patients with MF in Italy. Twenty-four-week findings confirmed ruxolitinib’s therapeutic effects and a favorable safety profile but also indicated that up to one third (25% to 40%) of patients receiving ruxolitinib could have been undertreated despite their clinical presentation necessitating higher doses. An interim analysis, conducted by the current authors, was commissioned to investigate ruxolitinib dosing patterns and correlations with clinical outcomes in patients who completed the first 12 months of follow-up or prematurely discontinued the ROMEI trial.¹

Patient symptom response and HRQoL during ruxolitinib treatment were assessed using the Myeloproliferative Neoplasm 10 total symptom score (MPN-10 TSS) and EuroQoL5-Dimension-5-Level (EQ-5D-5L) score. At data cutoff, a total of 359 patients with MF were eligible for inclusion in the analysis, of which 43.7% of patients began on ruxolitinib 20 mg twice daily, 20.6% on 15 mg twice daily, 22.3% on 10 mg twice daily, and only 12.0% on 5 mg twice. Patients were separated into groups based on ruxolitinib starting dosage: as expected (AsEx, n = 174) and lower than expected (LtEx, n = 132). Accordingly, 43% of the total patients initiated the treatment at a lower starting dose than expected, the investigators wrote.

Regarding specific patient hematologic parameters, such as platelet count and hemoglobin levels, these factors were slightly higher in the AsEx cohort than in the LtEx cohort. Dose adjustment and temporary interruption rates were similar between each group, but patients in the LtEx group had more permanent discontinuation.¹

Investigators next moved to an analysis of treatment response and patient HRQoL. They found that the proportion of patients with symptom response was higher in the AsEx group than in the LtEx group at 4 weeks (38.5% versus 27.3%) until 24 weeks (40.8% versus 39.4%). Notably, at 48 weeks, the proportion of responders was found to be similar between each group. Health improvements were indicated in both the AsEx and LtEx groups, as mean EQ-VAS scores representing patients’ health status had an upward trend at each patient visit.

Spleen response and survival outcomes were investigated under the umbrella of patient treatment response. At 24 and 48 weeks, spleen response rates were 50.0% (95% CI, 39.0-61.0) and 57.7% (95% CI, 46.0-68.8) in the AsEx group, respectively, and 30.2% (95% CI, 19.2-43.0) and 45.8% (95% CI, 31.4-60.8) in the LtEx group, respectively. For OS, a total of 23 (13.2%) and 27 (20.5%) patients in the AsEx and LtEx groups, respectively, died within the cutoff date. Furthermore, the estimated median survival time was not estimable (NE) in the AsEx group and 4.7 years (95% CI, 3.8-NE) in the LtEx group.¹

In their discussion, the investigators note that the accumulated evidence supports the meaningful positive impact of ruxolitinib at appropriate doses in patients with MF. They discuss that, as seen in ROMEI, initiation at recommended doses maximizes the OS benefits in patients, as observed in the AsEx and LtEx cohorts.¹

“Timely ruxolitinib treatment results in maximum patient benefits such as spleen size reduction, symptom relief, and improved OS,” the investigators concluded.¹

REFERENCES

1. Breccia M, Palandri F, Martelli M, et al. Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI). Cancer. 2025;131(7):e35801. doi:10.1002/cncr.25801

2. Halpern L. Patients with myelofibrosis and anemia treated with ruxolitinib have higher health care resource utilization, clinical burdens. Pharmacy Times. Published March 16, 2025. Accessed March 26, 2025. https://www.pharmacytimes.com/view/patients-with-myelofibrosis-and-anemia-treated-with-ruxolitinib-have-higher-health-care-resource-utilization-clinical-burdens

3. Guglielmelli P, Palandri F, Selleri C, et al. Adherence to ruxolitinib, an oral JAK1/2 inhibitor, in patients with myelofibrosis: Interim analysis from an Italian, prospective cohort study (ROMEI). Leukemia & Lymphoma. 2022;63(1):189-198. doi:10.1080/10428194.2021.1969388