CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma.
8000 Background: Lenalidomide (L) and rituximab (R) are active as single agents in follicular (FL) and other B-cell lymphomas, although combination strategies have not been previously assessed in a randomized fashion. Methods: CALGB 50401 is a randomized phase II study, initially designed to evaluate 3 regimens: R alone (375 mg/m2 weekly x 4), L alone (15 mg cycle 1, then escalated to 20 mg cycles 2-12, administered days 1-21 q 28 days x 12 cycles) or the combination of L+ R (other 2 arms combined). The R alone arm was discontinued due to slow accrual with 3 enrolled subjects. Eligibility included recurrent FL, prior therapy with rituximab alone or in combination, and TTP of ≥ 6 months from last rituximab dose. Prophylactic ASA or LMW heparin was recommended for patients at high risk for thrombosis. Results: Of 94 pts registered to L or LR, 89 (45 L and 44 LR) received at least one dose and had adequate data for analysis. Baseline characteristics include median age 63 (range 34-85) and 60% with intermediate- or high-risk FLIPI. Grade 3-4 adverse events (AE) were most commonly neutropenia (16% L,19% LR), fatigue (9% L, 14% LR) and thrombosis (16% - 7 pts L, 4% - 2 pts LR, p=0.158), and overall were seen in 49% (L) and 52% (LR) with 9% grade 4 in each arm. The full regimen was completed in 33% (L) and 59% (LR) of patients, with the difference due to more progressions or non-responders in the L group. In both arms about 19% of subjects discontinued therapy early due to AEs and dose intensity was over 80%. Objective response rates are L - 49% (13% CR) and LR - 75% (32% CR). With a median follow-up of 1.5 years (range 0.1- 3.6 years), median EFS is 1.2 years (L) and 2.0 years (LR), p=0.0063, log-rank test. Conclusions: Lenalidomide + rituximab is more active than lenalidomide alone in patients with recurrent FL with similar toxicity. A trend toward lower thrombosis risk with LR may relate to greater anti-tumor efficacy. The LR regimen warrants further study in FL including as a backbone for addition of novel agents in relapsed and frontline settings.