Hematologic and cytogenetic (CTG) response to lenalidomide (CC-5013) in patients with transfusion-dependent (TD) myelodysplastic syndrome (MDS) and chromosome 5q31.1 deletion: Results of the multicenter MDS-003 Study.

5 Background: Interstitial deletion of chromosome 5q31 is the most common CTG abnormality in MDS characterized by TD-anemia and megakaryocyte dysplasia. In a phase I/II trial in cytokine-unresponsive MDS, CC-5013 (RevLimid) yielded sustained transfusion-independence (TI) with CTG remission in 10/11 pts with del5q31 (List et al, NEJM 2005). We report results of a multicenter Phase II study evaluating the efficacy of CC-5013 in TD-MDS pts with del5q31.,Eligible pts had Low- or Int-1 risk MDS, TD-anemia (≥2U RBC/8 wks), ANC≥500/μl, and platelets≥50,000/μl. CC-5013 was given 10mg/d x21 po q4 wks [n=44] or 10mg daily [n=104] with dose ↓ as needed. IWG response was assessed after 24 wks with blinded central pathology and CTG review.,Among 148 pts with del5q31 (isolated, n=111; +other, n=37), median age was 71 (range, 37-95) with 66% females, confirmed TD-MDS in 146, mean MDS duration of 3.4 years (<1 to 20.7), and median RBC burden 5U/8 wks. Low/Int-1 MDS was confirmed in 122 pts (82%), with ineligible dx's of higher risk MDS [7], AML or other malignancy [3], or inadequate specimen [15]. In an intent-to-treat analysis, TI (≥56 d RBC transfusion-free + ≥1g/dl ↑ Hgb) was achieved in 93 (64%) TD-pts (95% CI: 55%-71%) with a median 3.9/dl Hgb ↑ (1.1-11.4) and 4 wk interval to response (0.3-19 wks). Among confirmed Low/Int-1 pts, 80 (66%) achieved TI vs 13/25 (52%; p=0.184) with other dx. TI rate was greater in pts with isolated del5q (69% vs 49%; p=0.003). CTG response (≥50↓ abnl metaphases) was achieved in 76% of TI patients with 55% CTG CRs. Pathologic CR was documented in 32/110 (29%) evaluable pts. After a median follow-up of 9.3 mos (4.2 to 14.8+), the median response duration is not reached with only 10 responders (9%) failing. Neutropenia (39%) or thrombocytopenia (35%) was the most common adverse event necessitating tx interruption or dose ↓. Nine patients progressed to RAEB±t [n=5] or AML [n=4], and 12 succumbed to disease complications [n=9] or neutropenic infection [n=3].,CC-5013 is highly effective in MDS pts with del5q31 with unprecedented hematologic and CTG remitting activity. [Table: see text].