Phase Ib study of avadomide (CC-122) in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma.

The multicenter, phase Ib CC-122-DLBCL-001 dose-expansion study (NCT02031419) explored the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC-122) plus rituximab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received avadomide 3 mg/day 5 days on/2 days off plus rituximab 375 mg/m on day 8 of cycle 1, day 1 of cycles 2 through 6, and day 1 of every third subsequent cycle for 2 years. Primary endpoints were safety and tolerability; preliminary efficacy was a secondary endpoint. A total of 68 patients were enrolled (DLBCL [ = 27], FL [ = 41; 31 lenalidomide-naïve, 10 lenalidomide-treated]). Median age was 62 years (range, 33-84 years), and patients had received a median of 3 (range, 1-8) prior regimens. Among patients with DLBCL, 66.7% had primary refractory disease (partial response or less to initial therapy). Among patients with FL, 65.9% were rituximab-refractory at study entry and 10.0% were lenalidomide-refractory. The most common any-grade avadomide-related adverse events (AEs) were neutropenia (63.2%), infections/infestations (23.5%), fatigue (22.1%), and diarrhea (19.1%). The most common grade 3/4 avadomide-related AEs were neutropenia (55.9%) infections/infestations (8.8%), and febrile neutropenia (7.4%). In patients with DLBCL, overall response rate (ORR) was 40.7% and median duration of response (mDOR) was 8.0 months. In patients with FL, ORR was 80.5% and mDOR was 27.6 months; response rates were similar in lenalidomide-naïve and -treated patients. Avadomide plus rituximab was well tolerated, and preliminary antitumor activity was observed in patients with R/R DLBCL and FL, including subgroups with typically poor outcomes. These results support further investigation of novel CELMoD agents in combination with rituximab in R/R DLBCL and FL.