Deutsches MDS-Forum - Duisburg 2008
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Final Results From A Phase I Combination Study of Lenalidomide and Azacitidine In Patients With Higher-risk Myelodysplastic Syndromes

Autor: Mikkael Sekeres, MD, Taussig Cancer Center, Cleveland Clinic, Ohio, USA
Quellenangabe: 2. Deutsches MDS-Forum - Duisburg 2008
Stand: 15.11.2008

Lenalidomide (LEN) and azacitidine (AZA) have demonstrated single agent activity in lower- and higher-risk MDS patients (pts). Response rates may be improved by combining LEN’s immunomodulatory, anti-angiogenic, and cytotoxic properties with AZA’s cytotoxic effects and its effects on DNA methyltransferase activity. We conducted a multicenter, Phase I trial. The aim was to determine the safety of combination therapy, defined as the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs, defined as Grade 3/4 non-hematologic toxicity per NCI CTC 3.0, or >50% neutrophil (ANC) or platelet (plt) drop without recovery by Day 56); efficacy was a secondary objective, using modified International Working Group response criteria. Pts with higher-risk MDS (IPSS score >1.5, or FAB or WHO classification with >5% myeloblasts) were enrolled using a "3+3" dose escalation desigh (see Table) from 6/06 through 5/08, with results reported through 7/08. Cycles lasted 28 days, to a maximum of 7 cycles. In all, 18 pts have been enrolled. The combination of LEN and AZA was well-tolerated, and early results suggest efficacy in advanced MDS superior to single drug therapy. The MTD will be discussed.