Azacitidine With or Without Lenalidomide in Higher Risk Myelodysplastic Syndrome & Low Blast Acute Myeloid Leukemia

Abstract

Standard treatment for higher risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast acute myeloid leukemia (AML) is azacitidine. In single arm studies, the addition of lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II clinical trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1 to 21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% CMML, 12% AML and 74% MDS. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median aza cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% AZA arm and 54% LEN AZA arm (p=0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup (MDS, AML or CMML) or IPSS-R. ORR was 57% in AZA arm and 69% in LEN AZA (p=0.14). There was no difference in progression free or overall survival between the arms (each p > 0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk MDS, CMML or low blast AML patients compared to treatment with azacitidine alone. This trial was registered at www.anzctr.org.au as ACTRN12610000271000. Funding: This study was supported by Celgene with grant funding for study conduct, Snowdome Foundation and the Victorian Epigenetic Group for funding support for molecular studies. Conflict of Interest Disclosure: MK, DH, JFS received research funding from Celgene MK and JFS are advisory board members for Celgene JFS is a member of speakers bureau for Celgene MH is an advisory board member for Takeda, Roche, MSD, Gilead, Janssen WS receives honoraria from Amgen and Novartis The remaining authors declare no conflict of interest; IC, KT, DZant, MW, MD, RE, SJ, TG, DZann, PB, WB. Ethics Approval Statement: Study design and treatment ALLG MDS4 was an open-label, multi-centre study conducted across 30 Australian sites. The study was reviewed and approved by the Human Research Ethics Committees of each centre and conducted according to the Declaration of Helsinki. All patients provided written informed consent prior to participation.