Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study

Abstract

We report the final 2-year end-of-study results from the first clinical trial investigating combination treatment with ruxolitinib and low-dose pegylated interferon-α2 (PEG-IFNα2). The study included 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEGIFNα2. The primary outcome was efficacy, based on hematologic parameters, quality of life measurements, and JAK2 V617F allele burden. We used the 2013 European LeukemiaNet and International Working Group- Myeloproliferative Neoplasms Research and Treatment response criteria, including response in symptoms, splenomegaly, peripheral blood counts, and bone marrow. Of 32 patients with polycythemia vera, ten (31%) achieved a remission which was a complete remission in three (9%) cases. Of 18 patients with myelofibrosis, eight (44%) achieved a remission; five (28%) were complete remissions. The cumulative incidence of peripheral blood count remission was 0.85 and 0.75 for patients with polycythemia vera and myelofibrosis, respectively. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score decreased from 22 [95% confidence interval (95% CI):, 16-29] at baseline to 15 (95% CI: 10-22) after 2 years. The median JAK2 V617F allele burden decreased from 47% (95% CI: 33-61%) to 12% (95% CI: 6-22%), and 41% of patients achieved a molecular response. The drop-out rate was 6% among patients with polycythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNα2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNα2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12.

Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature

“…Combination therapy may also permit lower doses, thus improving tolerability. The Phase II COMBI clinical trial evaluated ruxolitinib and pegylated interferon alfa-2a in 32 PV and 18 MF patients, of which 46 patients were intolerant of or refractory to pegylated interferon monotherapy [64]. There were no high-risk MF patients included in this trial, with the majority being low or intermediate-1 risk by DIPSS+.…”

New Perspectives on Polycythemia Vera: From Diagnosis to Therapy

“…As far as PV subjects are concerned, 9% achieved a complete and 22% a partial remission; in addition, the median JAK2 V617F burden decreased from 47% to 12%. Out of 36 patients previously intolerant to PEG-IFN alpha-2, 86% completed the study with acceptable toxicity [ 85 ].…”

The 2020 revision of the guidelines for the management of myeloproliferative neoplasms

“…There has been no available drug for the disease-modifying activity of PMF, and thus currently, treatment is aimed at improving anemia, reducing splenomegaly, and relieving disease-related symptoms [106]. However, recent trials using JAK inhibitors, interferons, and other emerging drugs have tried to demonstrate the effect on molecular responses, cytogenetic response, and marrow fibrosis [107][108][109]. Therefore, the response criteria were revised to evaluate not only the hematologic and clinical responses but also the molecular and cytogenetic responses (Table 8) [110].…”