Activity of Lenalidomide in a Phase II Single Institution Study in Non-Del(5q) Transfusion Dependent, Patients with Low and Intermediate-1 Risklower-Risk, Non-Del(5q) Myelodysplastic Syndromes (MDS))): Results From a Single-Institution Phase II Study

Abstract 4929

In a previous multi-center Phase II study, lenalidomide resulted in a 43% overall hematologic response with 26% of patients achieving transfusion independence (TI) among 214 non-del(5q) red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System (IPSS) lower-risk MDS (Raza et al Blood. 2008). A single institution follow-up trial was conducted in patients with low or Int-1 risk non-del(5q) MDS, a platelet count of >50, 000 and requiredat least 2 units of blood required in 8 weeks. Fifty-six patients received lenalidomide at a starting dose of 10 mg qday. There were 41 males and 15 females, and the median age was 71 years. By IPSS, 27 had low-risk disease and 22 had Int-1-risk disease, while IPSS could not be assigned for 7 patients. By cytogenetics, 38 patients had a normal karyotype, 12 showed abnormalities, while data could not be obtained for 4 patients due to culture failure. Morphologic classification consisted of: RA=17, RCMD=16, RARS=4, RCMD-RS=7, RARS-T=1 and RAEB-1=11. Median duration of MDS was 12 months (range 1–120 months). Median transfusion requirement was 2 units in 8 weeks prior to starting therapy. Median duration of lenalidomide therapy was 4 months (range, 1–36+ months). Treatment was generally well tolerated. The most common Grade 3/4 toxicity was myelosuppression, with 17 (30%) experiencing thrombocytopenia, 12/(21%) neutropenia and 1 leukopenia (2%). Other Grade 3/4 toxicities included diarrhea (7%) rash (2%), and fatigue (2%). At least one dose reduction was required for 33 (59%) patients. Intent-to-treat analysis showed hematologic response (HI) by the IWG-R criteria in 23 (41%) patients, no response in 25(44%) patients, and other failure in 8 (14%) patients. Among the 23 responders, 18 (32%) achieved TI. Median time to response was 2 cycles (6 weeks), with 6 patients responding in cycle 1, 9 in cycle 2, 5 in cycle 3 and 1 each in cycles 4, 5, 6, respectively. Median duration of response was 294 days (approximately 10 months), with durations ranging from 44+ days to 936+ days (+ indicates continuing response). We confirm in this 56-patient, single institution phase II study that lenalidomide has substantial clinical activity in transfusion-dependent, lower-risk non-del(5q) MDS, with results comparable to those previously reported in the multi-center phase II study.