Lenalidomide and Rituximab for the Initial Treatment of Chronic Lymphocytic Leukemia: Report of an Ongoing Study.

6583 Background: Lenalidomide (L) is an immunomodulatory agent and rituximab (R) a mAb with therapeutic activity in CLL. A phase II study was designed to evaluate this immunotherapy combination in treatment-naïve CLL pts with an indication for therapy. Methods: Pts were eligible if they had normal kidney function and no recent thromboembolic events. Pts started L at 2.5 mg/day (D) and could escalate to 5 mg/D on D8 to a maximum of 10 mg/D if tolerated. Pts received L 21/35 D for cycle (C) 1, then for 21/28 D for C2-7. R 50 mg/m2 D29, 325 mg/m2 D31, 375 mg/m2 D33, C1, then 375 mg/m2 weekly × 4 for C2 and on D1 for C3-7. Pts received allopurinol for tumor lysis prophylaxis. Results: 37 pts have been enrolled, 34 have demographic data and 30 evaluable for toxicity. Median age was 62 yrs (56 arm A, 73 arm B). 17/34 pts were Rai stage III-IV (40% arm A, 63% arm B). 16/31 pts had unmutated IgVH. FISH analysis revealed deletion of 17p (3 pts) and 11q (3 pts). The most common grade III/IV adverse events (AE) were neutropenia (18 pts), anemia (5 pts), and thrombocytopenia (4 pts). There were no cases of neutropenic fever, sepsis, or bleeding. Nonhematologic grade III/IV AEs included infection (3 pts arm B), rash (2 pts), and pulmonary embolus (PE) (1 pt per arm). The protocol was amended to include aspirin prophylaxis. Most frequent AEs (all grades) were the tumor flare reaction (TFR) (21/30), fatigue (19/30), and transient elevation of liver transaminases (25/30). TFR occurred in 15/17 pts (arm A) and 6/12 (arm B). Only a fraction of pts experienced TFR following the institution of R. Biochemical tumor lysis was observed in 2 pts without clinical tumor lysis. There have been no deaths. Median dose was 10 mg (arm A) and 5 mg (arm B) for pts that received > 3 cycles. 7 pts have been removed from study, 1 ineligible, 1 intolerance to R, 1 due to PCP, 1 with PE, 1 rash, and 1 thrombocytopenia. No pts have been removed for progressive disease. At interim analysis the criteria for continuing accrual to a total of 40 pts in each stratum were met with at least 2 clinical complete responses in each arm. Conclusions: Early results of the ongoing study suggest that immunotherapy with L and R is tolerable. TFR, a frequent AE did not usually occur following C1 possibly related to the use of R. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene