부산대학교 도서관

8541 Background: CFZ is a highly specific proteasome inhibitor with single agent activity in relapsed/refractory MM (ASH 2008). The purpose of this study is to evaluate the safety and activity of CFZ in combination with LEN and loDex.Methods: This phase Ib trial evaluates 4 dose levels (≥ 3 pts each) to define the maximum tolerated dose (MTD) of CFZ/LEN/loDex in relapsed/refractory MM pts who failed 1-3 prior therapies, including prior LEN or bortezomib (BTZ). CFZ IV 15- 20 mg/m2 (d1,2,8,9,15,16), LEN 10-20 mg po (d1-21) and loDex 40 mg po (d1, 8, 15, 22) in 28-day cycles (C). An additional 10-15 pts will be evaluated at the highest dose level reached. Dose limiting toxicity (DLT) has been defined as grade (G) ≥ 3 non- hematologic; G4 neutropenia for > 7d and/or neutropenic fever; G4 thrombocytopenia > 7d or G3-G4 thrombocytopenia in association with bleeding. Overall response (CR/sCR, VGPR/PR) is assessed by IWG criteria, with secondary assessment by modified EBMT criteria which includes MR.Results: 11 pts have been enrolled. 8/11 are evaluable for response and toxicity. Median prior lines of therapy was 2 (range 2-3). Prior therapies included DEX (8/8), BTZ (6/8), LEN (7/8), alkylators (6/8), anthracyclines (5/8), stem cell transplant (5/8), and thalidomide (1/8); 6/8 pts had received both LEN and BTZ. MTD has not yet been reached after the first 2 dose cohorts. No drug related SAEs or G3/4 treatment emergent AEs were reported. Responses to date with a median of 2 C (range 1-4) are shown below. Responses were rapid and occurred within the first 28-day cycle.Conclusions: CFZ/LEN/loDex in combination was well tolerated in the first 2 cohorts. There have been no myleosuppressive or renal DLTs. The combination has achieved early encouraging responses in pts who had failed both LEN and BTZ at doses well below the single agent MTD of either LEN or CFZ. Dose escalation is ongoing. Updated data will be presented at the meeting. [Table: see text] [Table: see text].