eJHaem (May 2022)

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

  • Loretta J. Nastoupil,
  • John Kuruvilla,
  • Julio C. Chavez,
  • Fontanet Bijou,
  • Thomas E. Witzig,
  • Armando Santoro,
  • Ian W. Flinn,
  • Carola Boccomini,
  • Vaishalee P. Kenkre,
  • Paolo Corradini,
  • Iris Isufi,
  • David J. Andorsky,
  • Leonard M. Klein,
  • Daniel R. Greenwald,
  • Randeep Sangha,
  • Frank Shen,
  • Patrick Hagner,
  • Yan Li,
  • Juergen Dobmeyer,
  • Nian Gong,
  • Shailaja Uttamsingh,
  • Michael Pourdehnad,
  • Vincent Ribrag

DOI
https://doi.org/10.1002/jha2.394
Journal volume & issue
Vol. 3, no. 2
pp. 394 – 405

Abstract

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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/m2 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.

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