Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis
Abstract Interferon‐α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation‐mediated toxicity, leading to treatment discontinuation in 10‐30% of patients. Ruxolitinib, a po...
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2018-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1619 |
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| author | Stine Ulrik Mikkelsen Lasse Kjær Mads Emil Bjørn Trine Alma Knudsen Anders Lindholm Sørensen Christen Bertel Lykkegaard Andersen Ole Weis Bjerrum Nana Brochmann Daniel El Fassi Torben A. Kruse Thomas Stauffer Larsen Hans Torben Mourits‐Andersen Claus Henrik Nielsen Niels Pallisgaard Mads Thomassen Vibe Skov Hans Carl Hasselbalch |
| author_facet | Stine Ulrik Mikkelsen Lasse Kjær Mads Emil Bjørn Trine Alma Knudsen Anders Lindholm Sørensen Christen Bertel Lykkegaard Andersen Ole Weis Bjerrum Nana Brochmann Daniel El Fassi Torben A. Kruse Thomas Stauffer Larsen Hans Torben Mourits‐Andersen Claus Henrik Nielsen Niels Pallisgaard Mads Thomassen Vibe Skov Hans Carl Hasselbalch |
| author_sort | Stine Ulrik Mikkelsen |
| collection | DOAJ |
| description | Abstract Interferon‐α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation‐mediated toxicity, leading to treatment discontinuation in 10‐30% of patients. Ruxolitinib, a potent anti‐inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon‐α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon‐α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low‐/intermediate‐1‐risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon‐α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow‐up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty‐seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon‐α2 and ruxolitinib is efficacious in patients with low‐/intermediate‐1‐risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients. |
| format | Article |
| id | doaj-art-ad5bd37c4a634aecb9bd94c778e184c8 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-ad5bd37c4a634aecb9bd94c778e184c82025-08-20T01:58:43ZengWileyCancer Medicine2045-76342018-08-01783571358110.1002/cam4.1619Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosisStine Ulrik Mikkelsen0Lasse Kjær1Mads Emil Bjørn2Trine Alma Knudsen3Anders Lindholm Sørensen4Christen Bertel Lykkegaard Andersen5Ole Weis Bjerrum6Nana Brochmann7Daniel El Fassi8Torben A. Kruse9Thomas Stauffer Larsen10Hans Torben Mourits‐Andersen11Claus Henrik Nielsen12Niels Pallisgaard13Mads Thomassen14Vibe Skov15Hans Carl Hasselbalch16Department of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Rigshospitalet Copenhagen DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Herlev University Hospital Copenhagen DenmarkDepartment of Clinical Genetics Odense University Hospital Odense DenmarkDepartment of Hematology Odense University Hospital Odense DenmarkDepartment of Hematology South‐West Jutlandic Hospital Esbjerg DenmarkInstitute for Inflammation Research Rigshospitalet Copenhagen DenmarkDepartment of Pathology Zealand University Hospital Roskilde DenmarkDepartment of Clinical Genetics Odense University Hospital Odense DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkDepartment of Hematology Zealand University Hospital Roskilde DenmarkAbstract Interferon‐α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation‐mediated toxicity, leading to treatment discontinuation in 10‐30% of patients. Ruxolitinib, a potent anti‐inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon‐α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon‐α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low‐/intermediate‐1‐risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon‐α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow‐up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty‐seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon‐α2 and ruxolitinib is efficacious in patients with low‐/intermediate‐1‐risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.https://doi.org/10.1002/cam4.1619combination therapyinterferon‐alphamyeloproliferative neoplasmspolycythemia veraprimary myelofibrosisruxolitinib |
| spellingShingle | Stine Ulrik Mikkelsen Lasse Kjær Mads Emil Bjørn Trine Alma Knudsen Anders Lindholm Sørensen Christen Bertel Lykkegaard Andersen Ole Weis Bjerrum Nana Brochmann Daniel El Fassi Torben A. Kruse Thomas Stauffer Larsen Hans Torben Mourits‐Andersen Claus Henrik Nielsen Niels Pallisgaard Mads Thomassen Vibe Skov Hans Carl Hasselbalch Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis Cancer Medicine combination therapy interferon‐alpha myeloproliferative neoplasms polycythemia vera primary myelofibrosis ruxolitinib |
| title | Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| title_full | Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| title_fullStr | Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| title_full_unstemmed | Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| title_short | Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| title_sort | safety and efficacy of combination therapy of interferon α2 and ruxolitinib in polycythemia vera and myelofibrosis |
| topic | combination therapy interferon‐alpha myeloproliferative neoplasms polycythemia vera primary myelofibrosis ruxolitinib |
| url | https://doi.org/10.1002/cam4.1619 |
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