A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms
Autor: | Sherry Pierce, Lingsha Zhou, Graciela M. Nogueras-Gonzalez, Gautam Borthakur, Rita Assi, Naveen Pemmaraju, Srdan Verstovsek, Keyur P. Patel, Courtney D. DiNardo, Romany Gergis, Rajyalakshmi Luthra, Elias Jabbour, Prithviraj Bose, Guillermo Garcia-Manero, Juliana E. Hidalgo-Lopez, Carlos E. Bueso-Ramos, Hagop M. Kantarjian, Jorge E. Cortes, Carla Tuttle, Xuemei Wang, Zeev Estrov, Naval Daver, Tapan M. Kadia |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male Ruxolitinib medicine.medical_specialty Anemia Gastroenterology Drug Administration Schedule New onset 03 medical and health sciences 0302 clinical medicine Pharmacotherapy hemic and lymphatic diseases Internal medicine Nitriles medicine Humans In patient Survival analysis Aged Aged 80 and over business.industry Hematology Middle Aged medicine.disease Myelodysplastic-Myeloproliferative Diseases Survival Analysis Thrombocytopenia Discontinuation Surgery Clinical trial Pyrimidines Treatment Outcome 030220 oncology & carcinogenesis Azacitidine Pyrazoles Drug Therapy Combination Female business 030215 immunology medicine.drug |
Zdroj: | American journal of hematology. 93(2) |
ISSN: | 1096-8652 |
Popis: | Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m2 (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m2 (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts. Thirty-five patients were treated (MDS/MPN-U, n =14; CMML, n =17; aCML, n =4), with a median follow-up of 15.2 months (range, 1.0–41.5). All patients were evaluable by the 2015 international consortium proposal of response criteria for MDS/MPNs (ICP MDS/MPN) and 20 (57%) responded. Nine patients (45%) responded after the addition of azacytidine. A greater than 50% reduction in palpable splenomegaly at 24 weeks was noted in 9/14 (64%) patients. Responders more frequently were JAK2-mutated (P = 0.02) and had splenomegaly (P = 0.03) compared to non-responders. New onset grade 3/4 anemia and thrombocytopenia occurred in 18 (51%) and 19 (54%) patients, respectively, but required therapy discontinuation in only 1 (3%) patient. Patients with MDS/MPN-U had better median survival compared to CMML and aCML (26.5 vs 15.1 vs 8 months; P = 0.034). The combination of ruxolitinib and azacytidine was well-tolerated with an ICP MDS/MPN-response rate of 57% in patients with MDS/MPNs. The survival benefit was most prominent in patients with MDS/MPN-U. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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