The combination of interferon and ruxolitinib may be a treatment option for newly diagnosed polycythemia vera (PV), “which could present a long-term approach with low-dose interferon or treatment pauses for these patients,” according to the study authors. The results of the study were presented at the 2022 American Society of Hematology (ASH) Annual Meeting.
Around 20% to 30% of patients are intolerant or show limited response to interferon, thus combination of interferon and ruxolitinib may be more efficacious for patients. Previous studies suggest that after achieving deep hematologic and molecular response, treatment pause may be possible following interferon treatment.
The COMBI-I trial demonstrated the efficacy of interferon-alpha-2a and ruxolitinib in patients with PV and myelofibrosis who were mostly intolerant or refractory to interferon monotherapy. The COMBI-II trial assessed this treatment combination in newly diagnosed PV, and the results presented at ASH reflect a preplanned interim analysis after at least one year of treatment. Researchers sought to determine whether an initial high-intensity regimen to control PV could allow for treatment pause or low-dose interferon monotherapy.
Patients were pretreated according to normal clinical standard with phlebotomies and hydroxyurea for high-risk patients before initiation of combination treatment. Hydroxyurea was withheld one week before initiation of treatment, and patients with severe kidney, liver, or heart disease were excluded.
A total of 25 patients with PV were included between 2019 and 2021, with a median age of 70 years, a little more than half (n=14) were female. Most patients (n=19) were high risk, and five had prior thrombosis. Median time from referral to treatment was 67 days, and median follow-up was 21 months. Initial therapy included interferon 45 μg subcutaneously (SC) weekly and ruxolitinib 10 mg twice daily.
At evaluation, 13 patients completed 24 months of treatment, while 24 completed 12 months. One patients withdrew due to development of myelofibrosis 10 months after beginning treatment, and another patient was diagnosed with follicular lymphoma nine months of treatment started. One patient had acute myocardial infarction.
No grade 3/4 infections occurred. At follow-up, 19 patients were still receiving the combination therapy. Grade 1/2 anemia occurred frequently and was managed with dose reductions. At follow-up, patients were receiving the following median treatment doses: ruxolitinib 5 mg twice daily and interferon 45 μg SC weekly.
There was a high rate of hematologic response one month into treatment. Three patients required phlebotomy after two weeks of treatment.
The JAK2V617F allele burden was significantly reduced three months after treatment, decreasing from a median of 47% (95% CI, 35-59) at baseline to 6% (95% CI, 3-12) after two years of treatment. Four patients had a JAK2V617F allele burden <1%, and seven had a JAK2V617F allele burden <5% at the latest measurement since treatment initiation. No significant difference in JAK2V617F allele burden was observed between referral and initiation of the combination treatment.
Sørensen ALL, Skov V, Kjær L, et al. Combination therapy with ruxolitinib and interferon in newly diagnosed patients with polycythemia vera. Abstract #3029. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.