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
Affiliations
Loretta J. Nastoupil
Department of Lymphoma and Myeloma Division of Cancer Medicine MD Anderson Cancer Center The University of Texas Houston Texas USA
John Kuruvilla
Division of Medical Oncology and Hematology Princess Margaret Cancer Centre University of Toronto Toronto Ontario Canada
Julio C. Chavez
H. Lee Moffitt Cancer Center and Research Institute Tampa Florida USA
Fontanet Bijou
Institut Bergonié Bordeaux Cedex France
Thomas E. Witzig
Mayo Clinic Rochester Minnesota USA
Armando Santoro
Department of Biomedical Sciences Pieve Emanuele Milan Humanitas University Italy ‐IRCCS Humanitas Research Hospital‐ Humanitas Cancer Center Rozzano Milan Italy
Ian W. Flinn
Sarah Cannon Research Institute Nashville Tennessee USA
Carola Boccomini
SC Ematologia ASOU Città della Salute e della Scienza di Torino Turin Italy
Vaishalee P. Kenkre
Division of Hematology and Oncology University of Wisconsin Madison Wisconsin USA
Paolo Corradini
IRCCS Istituto Nazionale dei Tumori University of Milano Milano Italy
Iris Isufi
Yale Cancer Center New Haven Connecticut USA
David J. Andorsky
Rocky Mountain Cancer Centers The US Oncology Network Boulder Colorado USA
Leonard M. Klein
Illinois Cancer Specialists The US Oncology Network Niles Illinois USA
Daniel R. Greenwald
Cancer Center of Santa Barbara Santa Barbara California USA
Randeep Sangha
Cross Cancer Institute Edmonton Alberta Canada
Frank Shen
Bristol Myers Squibb Princeton New Jersey USA
Patrick Hagner
Bristol Myers Squibb Princeton New Jersey USA
Yan Li
Bristol Myers Squibb Princeton New Jersey USA
Juergen Dobmeyer
Centre for Innovation and Translational Research Europe (CITRE) Bristol‐Myers Squibb Company Seville Spain
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.
