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, 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, Advocate Aurora HealthFollow
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.
Nian Gong, Bristol Myers Squibb Princeton New Jersey USA.
Shailaja Uttamsingh, Bristol Myers Squibb Princeton New Jersey USA.
Michael Pourdehnad, Bristol Myers Squibb Princeton New Jersey USA.
Vincent Ribrag, Institut Gustave Roussy Villejuif France.


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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