Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma
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 rec...
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| Language: | English |
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Wiley
2022-05-01
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| Series: | eJHaem |
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| Online Access: | https://doi.org/10.1002/jha2.394 |
| _version_ | 1797739969678147584 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Loretta J. Nastoupil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T14:05:50Z |
| format | Article |
| id | doaj.art-893d9f4d49df48ae90782ee3c1a4ed6c |
| institution | Directory Open Access Journal |
| issn | 2688-6146 |
| language | English |
| last_indexed | 2024-03-12T14:05:50Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | eJHaem |
| spelling | doaj.art-893d9f4d49df48ae90782ee3c1a4ed6c2023-08-21T14:11:09ZengWileyeJHaem2688-61462022-05-013239440510.1002/jha2.394Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphomaLoretta J. Nastoupil0John Kuruvilla1Julio C. Chavez2Fontanet Bijou3Thomas E. Witzig4Armando Santoro5Ian W. Flinn6Carola Boccomini7Vaishalee P. Kenkre8Paolo Corradini9Iris Isufi10David J. Andorsky11Leonard M. Klein12Daniel R. Greenwald13Randeep Sangha14Frank Shen15Patrick Hagner16Yan Li17Juergen Dobmeyer18Nian Gong19Shailaja Uttamsingh20Michael Pourdehnad21Vincent Ribrag22Department of Lymphoma and Myeloma Division of Cancer Medicine MD Anderson Cancer Center The University of Texas Houston Texas USADivision of Medical Oncology and Hematology Princess Margaret Cancer Centre University of Toronto Toronto Ontario CanadaH. Lee Moffitt Cancer Center and Research Institute Tampa Florida USAInstitut Bergonié Bordeaux Cedex FranceMayo Clinic Rochester Minnesota USADepartment of Biomedical Sciences Pieve Emanuele Milan Humanitas University Italy ‐IRCCS Humanitas Research Hospital‐ Humanitas Cancer Center Rozzano Milan ItalySarah Cannon Research Institute Nashville Tennessee USASC Ematologia ASOU Città della Salute e della Scienza di Torino Turin ItalyDivision of Hematology and Oncology University of Wisconsin Madison Wisconsin USAIRCCS Istituto Nazionale dei Tumori University of Milano Milano ItalyYale Cancer Center New Haven Connecticut USARocky Mountain Cancer Centers The US Oncology Network Boulder Colorado USAIllinois Cancer Specialists The US Oncology Network Niles Illinois USACancer Center of Santa Barbara Santa Barbara California USACross Cancer Institute Edmonton Alberta CanadaBristol Myers Squibb Princeton New Jersey USABristol Myers Squibb Princeton New Jersey USABristol Myers Squibb Princeton New Jersey USACentre for Innovation and Translational Research Europe (CITRE) Bristol‐Myers Squibb Company Seville SpainBristol Myers Squibb Princeton New Jersey USABristol Myers Squibb Princeton New Jersey USABristol Myers Squibb Princeton New Jersey USAInstitut Gustave Roussy Villejuif FranceAbstract 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.https://doi.org/10.1002/jha2.394avadomideCELMoDdiffuse large B‐cell lymphomafollicular lymphoma |
| spellingShingle | 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 Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma eJHaem avadomide CELMoD diffuse large B‐cell lymphoma follicular lymphoma |
| title | Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma |
| title_full | Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma |
| title_fullStr | Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma |
| title_full_unstemmed | Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma |
| title_short | Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma |
| title_sort | phase ib study of avadomide cc 122 in combination with rituximab in patients with relapsed refractory diffuse large b cell lymphoma and follicular lymphoma |
| topic | avadomide CELMoD diffuse large B‐cell lymphoma follicular lymphoma |
| url | https://doi.org/10.1002/jha2.394 |
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