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Ferrata Storti Foundation
Haematologica 2020 Volume 105(9):2262-2272
Myeloproliferative Neoplasms
Ruxolitinib and interferon-a2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study
Anders Lindholm Sørensen,1,2 Stine Ulrik Mikkelsen,3,4 Trine Alma Knudsen,1 Mads Emil Bjørn,5 Christen Lykkegaard Andersen,3,6 Ole Weis Bjerrum,3 Nana Brochmann,1 Dustin Andersen Patel,1,2 Lise Mette Rahbek Gjerdrum,7 Daniel El Fassi,5 Torben A. Kruse,8 Thomas Stauffer Larsen,9 Hans Torben Mourits- Andersen,10 Claus Henrik Nielsen,2 Christina Ellervik,5,11,12 Niels Pallisgaard,7 Mads Thomassen,8 Lasse Kjær,1 Vibe Skov1 and Hans Carl Hasselbalch1
1Department of Hematology, Zealand University Hospital, Roskilde, Denmark; 2Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 3Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 4Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark; 5Herlev University Hospital, Copenhagen, Denmark; 6Department of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 7Department of Pathology, Zealand University Hospital, Roskilde, Denmark; 8Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; 9Department of Hematology, Odense University Hospital, Odense, Denmark; 10Department of Hematology, South-West Jutlandic Hospital, Esbjerg, Denmark; 11Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA and 12Data and Development Support, Region Zealand, Sorø, Denmark
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-a2 (PEG-IFNa2). The study includ- ed 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEG- IFNα2. The primary outcome was efficacy, based on hematologic parame- ters, 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 poly- cythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNa2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNa2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellular- ity and fibrosis, decreased JAK2 V617F burden, and reduced symptom bur- den with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12.
Correspondence:
ANDERS LINDHOLM SØRENSEN
anderslindholmsorensen@hotmail.com
Received: August 18, 2019. Accepted: December 20, 2019. Pre-published: January 16, 2020.
doi:10.3324/haematol.2019.235648 ©2020 Ferrata Storti Foundation
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