Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase
John Mascarenhas, Raajit K. Rampal, Heidi Kosiorek, Rupali Bhave, Elizabeth O. Hexner, Eunice S. Wang, Aaron T. Gerds, Camille N. Abboud, Marina Kremyanskaya, Dimitry Berenzon, Olatoyosi Odenike, Noushin Farnoud, Aishwarya Krishnan, Rona Singer Weinberg, Erin McGovern, Mohamed E. Salama, Vesna Najfeld, Juan S. Medina-Martínez, Juan Arango Ossa, Max F. Levine, Yangyu Zhou, Lonette Sandy, Mark Heaney, Ross L. Levine, Ruben A. Mesa, Amylou C. Dueck, Ronald Hoffman
Abstract
Myeloproliferative neoplasms (MPN) that have evolved into accelerated or blast phase disease (MPN-AP/BP) have poor outcomes with limited treatment options and therefore represent an urgent unmet need. We have previously demonstrated in a multicenter, phase 1 trial conducted through the Myeloproliferative Neoplasms Research Consortium that the combination of ruxolitinib and decitabine is safe and tolerable and is associated with a favorable overall survival (OS). In this phase 2 trial, 25 patients with MPN-AP/BP were treated at the recommended phase 2 dose of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle. Nineteen patients died during the study follow-up. The median OS for all patients on study was 9.5 months (95% confidence interval, 4.3-12.0). Overall response rate (complete remission + incomplete platelet recovery + partial remission) was 11/25 (44%) and response was not associated with improved survival. We conclude that the combination of decitabine and ruxolitinib was well tolerated, demonstrated favorable OS, and represents a therapeutic option for this high-risk patient population. This trial was registered at www.clinicaltrials.gov as #NCT02076191.