1. Combination therapy with ruxolitinib and pegylated interferon alfa-2a in newly diagnosed patients with polycythemia vera.
- Author
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Sørensen AL, Skov V, Kjær L, Bjørn ME, Eickhardt-Dalbøge CS, Larsen MK, Nielsen CH, Thomsen C, Rahbek Gjerdrum LM, Knudsen TA, Ellervik C, Overgaard UM, Andersen CL, and Hasselbalch H
- Subjects
- Humans, Aged, Male, Female, Middle Aged, Treatment Outcome, Aged, 80 and over, Interferon-alpha therapeutic use, Interferon-alpha administration & dosage, Polycythemia Vera drug therapy, Polycythemia Vera diagnosis, Nitriles therapeutic use, Pyrazoles therapeutic use, Pyrazoles administration & dosage, Polyethylene Glycols therapeutic use, Recombinant Proteins therapeutic use, Pyrimidines therapeutic use, Janus Kinase 2 genetics
- Abstract
Abstract: We report the 2-year end-of-study results from the phase 2 COMBI II clinical trial investigating the combination treatment of ruxolitinib and low-dose pegylated interferon alfa-2a in patients with newly diagnosed polycythemia vera (PV). The primary outcome was safety and key secondary endpoints were efficacy, based on hematologic parameters, quality-of-life measurements, and JAK2V617F variant allele frequency (VAF). We used the 2013 European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research remission criteria. The remission criteria included remissions in symptoms, splenomegaly, peripheral blood counts, and bone marrow. We included 25 patients with PV with a median age of 70 years; 5 of those had prior thromboembolic events and 3 had computed tomography-verified splenomegaly. Two patients stopped both study drugs; 1 of these due to progression to post-PV myelofibrosis, the only one with a grade 3 infection. No events of herpes zoster infections were observed. None of the patients discontinued treatment due to psychiatric symptoms. The peripheral blood cell count remission rate was 92% at 24 months. Using the 2013 European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research remission criteria, 14 (56%) achieved remission at 24 months; 3 (12%) achieved complete remission and 11 (44%) achieved partial remission. The following items from the Myeloproliferative Neoplasm Symptom Total Symptom Score were significantly reduced: abdominal discomfort, night sweats, itching, and bone pain. 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. In conclusion, combination treatment improved cell counts; bone marrow cellularity, and fibrosis; and decreased JAK2V617F VAF; with acceptable toxicity in patients with PV. The trial was registered at www.clinicaltrialsregister.eu as #EudraCT2018-004150-13., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
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