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

Abstract

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. Methods: 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. Response: 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]. Conclusions: CC-5013 is highly effective in MDS pts with del5q31 with unprecedented hematologic and CTG remitting activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene