Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma. Issue 2 (14th February 2022)

• Record Type: Journal Article
• Authors: Nastoupil, Loretta J.; Kuruvilla, John; Chavez, Julio C.; Bijou, Fontanet; Witzig, Thomas E.; Santoro, Armando; Flinn, Ian W.; Boccomini, Carola; Kenkre, Vaishalee P.; Corradini, Paolo; Isufi, Iris; Andorsky, David J.; Klein, Leonard M.; Greenwald, Daniel R.; Sangha, Randeep; Shen, Frank; Hagner, Patrick; Li, Yan; Dobmeyer, Juergen; Gong, Nian; Uttamsingh, Shailaja; Pourdehnad, Michael; Ribrag, Vincent
• Is Part Of: EJHaem. Volume 3:Issue 2(2022)
• Page Start: 394
• Page End: 405
• Publication Date: 2022-02-14
• Subjects: avadomide -- CELMoD -- diffuse large B‐cell lymphoma -- follicular lymphoma; Hematology -- Periodicals; 616.15
• DOI: 10.1002/jha2.394
• Languages: English
• ISSNs: 2688-6146

Abstract

Abstract: 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 2 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 [ n = 27], FL [ n = 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.