Ruxolitinib Plus Pegylated Interferon Alfa-2a Show Promise in Newly Diagnosed Polycythemia Vera

Ruxolitinib (Jakafi; Incyte Corp) in combination with pegylated interferon alfa-2a demonstrated efficacy and tolerability in patients with newly diagnosed polycythemia vera (PV). According to the 2-year end-of-study results from the phase 2 COMBI 2 clinical trial (EudraCT2018-004150-13), the treatment improved cell counts, bone marrow cellularity, and fibrosis in patients with PV.¹

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV. Image Credit: © MdBabul - stock.adobe.com

PV is a chronic, progressive myeloproliferative neoplasm characterized by the overproduction of red blood cells. The excess cells thicken the blood, slowing its flow and contributing to serious complications, such as blood clots. Almost all patients with PV have the JAK2V617F mutations, and the JAK2V617F variant allele frequency (VAF) is key for determining outcomes, including thrombosis and progression to myelofibrosis.^2-4

Ruxolitinib is a Janus kinase inhibitor approved by the FDA in 2011 and is indicated for the treatment of patients with high-risk MF with reduced abnormal expression of PF4, which can lead to decreased fibrosis. It is additionally indicated as a second-line treatment of PV for patients who have an inadequate response to or cannot tolerate hydroxyurea. In the COMBI 2 trial, researchers assessed the efficacy of ruxolitinib in combination with pegylated interferon alfa-2a (peg-IFN-α2a) (Pegasys ProClick; Genentech), an injection commonly used to treat hepatitis B and C infections. According to data from prior studies, peg-IFN-α2a has been shown to induce durable hematologic and molecular remissions in patients with PV. However, approximately 20% to 40% of patients are intolerant or show limited response to peg-IFN-α2a.^5-8

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV in an effort to counterbalance intolerance to peg-IFN-α2a. The primary end point was safety, with secondary end points including efficacy, based on hematologic parameters, quality-of-life measurements, and JAK2V617F variant allele frequency (VAF).⁸

They assessed 25 patients with PV with a median age of 70 years; 5 who had prior thromboembolic events and 3 who had computed tomography–verified splenomegaly. Prior to initiation of the combination therapy, patients were pretreated with phlebotomies, or hydroxyurea at the researcher’s discretion. After pretreatment, they received peg-IFN-α2a 45 μg per week and oral ruxolitinib 10 mg twice daily.⁸

Using the 2013 European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research remission criteria, the researchers measured remission in symptoms, splenomegaly, peripheral blood counts, and bone marrow. According to the data, the total rate of blood cell count remission at 24 months was 92%. Additionally, 56% achieved remission at 24 months, 12% achieved complete remission, and 44% achieved partial remission. There were also significant reductions in abdominal discomfort, night sweats, itching, and bone pain.⁸

Data showed that the median JAK2V617F VAF decreased from 47% (95% confidence interval [CI], 35-59) to 7% (95% CI, 3-15), and 60% of patients achieved molecular remission.⁸

By effectively managing hematologic parameters and reducing the JAK2V617F variant allele frequency, ruxolitinib and low-dose peg-IFN-α2a could offer a well-tolerated, effective treatment pathway for patients. These findings underscore the importance of novel therapeutic combinations in PV and aid in refining treatment approaches for patients.

REFERENCES

1. Combination therapy with interferon-alpha2a and ruxolitinib in newly diagnosed patients with polycythemia vera. a danish safety and efficacy study. EudraCT Number: 2018-004150-13. October 31, 2018. Accessed October 31, 2024. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004150-13/DK

2. Polycythemia vera. Mayo Clinic. February 11, 2022. Accessed October 31, 2024. https://www.mayoclinic.org/diseases-conditions/polycythemia-vera/symptoms-causes/syc-20355850

3. Polycythemia vera (pv). MPN Research Foundation. Accessed October 31, 2024. https://mpnresearchfoundation.org/polycythemia-vera-pv/

4. Moliterno A, Kaizer H, Reeves B. Jak2 v617f allele burden in polycythemia vera: burden of proof. Blood. April 20, 2023. doi:10.1182/blood.2022017697

5. Study finds ruxolitinib may slow fibrosis progression in myelofibrosis. Pharmacy Times. September 24, 2024. Accessed October 31, 2024. https://www.pharmacytimes.com/view/study-finds-ruxolitinib-may-slow-fibrosis-progression-in-myelofibrosis

6. Pegasys proclick (subcutaneous). Drugs.com. February 23, 2024. Accessed October 31, 2024. https://www.drugs.com/cons/pegasys-proclick.html

7. Masarova L, Patel KP, Newberry KJ, et al. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. April 2017. doi:10.1016/S2352-3026(17)30030-3

8. Sørensen A, Skov V, Kjær L, et al. Combination therapy with ruxolitinib and pegylated interferon alfa-2a in newly diagnosed patients with polycythemia vera. Blood Adv. October 15, 2024. doi:10.1182/bloodadvances.2024013170