Safety and efficacy of combined ruxolitinib and decitabine in accelerated and blast-phase myeloproliferative neoplasms Journal Article
| Authors: | Rampal, R. K.; Mascarenhas, J. O.; Kosiorek, H. E.; Price, L.; Berenzon, D.; Hexner, E.; Abboud, C. N.; Kremyanskaya, M.; Singer Weinberg, R.; Salama, M. E.; Menghrajani, K.; Najfeld, V.; Sandy, L.; Heaney, M. L.; Levine, R. L.; Mesa, R. A.; Dueck, A. C.; Goldberg, J. D.; Hoffman, R. |
| Article Title: | Safety and efficacy of combined ruxolitinib and decitabine in accelerated and blast-phase myeloproliferative neoplasms |
| Abstract: | Myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to evolve into accelerated and blast-phase disease (MPN-AP/BP), carrying a dismal prognosis. Conventional antileukemia therapy has limited efficacy in this setting. Thus, MPN-AP/BP is an urgent unmet clinical need. Modest responses to hypomethylating agents and single-agent ruxolitinib have been reported. More recently, combination of ruxolitinib and decitabine has demonstrated synergistic in vitro activity in human and murine systems. These observations led us to conduct a phase 1 study to explore the safety of combined decitabine and dose-escalated ruxolitinib in patients with MPN-AP/BP. A total of 21 patients were accrued to this multicenter study. Ruxolitinib was administered at doses of 10, 15, 25, or 50 mg twice daily in combination with decitabine (20 mg/m2 per day for 5 days) in 28-day cycles. The maximum tolerated dose was not reached. The most common reasons for study discontinuation were toxicity/adverse events (37%) and disease progression (21%). Fourteen patients died during study treatment period or follow-up. The median overall survival for patients on study was 7.9 months (95% confidence interval, 4.1-not reached). Among evaluable patients, the overall response rate by protocol-defined criteria (complete remission with incomplete count recovery + partial remission) was 9/17 (53%) and by intention-to-treat analysis was 9/21 (42.9%). The combination of decitabine and ruxolitinib was generally well tolerated by patients with MPN-AP/BP and demonstrates potentially promising clinical activity. A phase 2 trial evaluating the efficacy of this combination regimen is ongoing within the Myeloproliferative Disorder Research Consortium. © 2018 by The American Society of Hematology. |
| Journal Title: | Blood Advances |
| Volume: | 2 |
| Issue: | 24 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2018-12-26 |
| Start Page: | 3572 |
| End Page: | 3580 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2018019661 |
| PROVIDER: | scopus |
| PMCID: | PMC6306885 |
| PUBMED: | 30563881 |
| DOI/URL: | |
| Notes: | Blood Adv -- Export Date: 2 January 2019 -- Article -- Source: Scopus C2 - 30563881 |
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