A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms

Rita Assi, Hagop M. Kantarjian, Guillermo Garcia-Manero, Jorge E. Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D. Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi LuthraJuliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver

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16 Scopus citations

Abstract

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 =.02) and had splenomegaly (P =.03) compared to nonresponders. 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 =.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.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalAmerican Journal of Hematology
Volume93
Issue number2
DOIs
StatePublished - Feb 1 2018

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ASJC Scopus subject areas

  • Hematology

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Assi, R., Kantarjian, H. M., Garcia-Manero, G., Cortes, J. E., Pemmaraju, N., Wang, X., Nogueras-Gonzalez, G., Jabbour, E., Bose, P., Kadia, T., Dinardo, C. D., Patel, K., Bueso-Ramos, C., Zhou, L., Pierce, S., Gergis, R., Tuttle, C., Borthakur, G., Estrov, Z., ... Daver, N. (2018). A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms. American Journal of Hematology, 93(2), 277-285. https://doi.org/10.1002/ajh.24972