Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3
Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. Aft...
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/8/e007118.full |
| _version_ | 1797728965811503104 |
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| author | Daniel J DeAngelo Yi Lin Roch Houot Marion Subklewe Petra C Schuberth Michael R Bishop Nicolas Boissel Dimitrios Tzachanis Jae H Park Monique C Minnema Thibaut Leguay Mehrdad Abedi Bijal D Shah Ryan D Cassaday Olalekan O Oluwole Aaron C Logan Max S Topp Kristen M O'Dwyer Martha L Arellano Maria R Baer Gary J Schiller William G Wierda Patrick J Stiff Deepa Jeyakumar Daqin Mao Sabina Adhikary Lang Zhou Rita Damico Khalid Armin Ghobadia |
| author_facet | Daniel J DeAngelo Yi Lin Roch Houot Marion Subklewe Petra C Schuberth Michael R Bishop Nicolas Boissel Dimitrios Tzachanis Jae H Park Monique C Minnema Thibaut Leguay Mehrdad Abedi Bijal D Shah Ryan D Cassaday Olalekan O Oluwole Aaron C Logan Max S Topp Kristen M O'Dwyer Martha L Arellano Maria R Baer Gary J Schiller William G Wierda Patrick J Stiff Deepa Jeyakumar Daqin Mao Sabina Adhikary Lang Zhou Rita Damico Khalid Armin Ghobadia |
| author_sort | Daniel J DeAngelo |
| collection | DOAJ |
| description | Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.Methods Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.Results Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7–58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).Conclusions In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel. |
| first_indexed | 2024-03-12T11:21:56Z |
| format | Article |
| id | doaj.art-6d2eb34905f7419ca7f3a7451cc9953e |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-12T11:21:56Z |
| publishDate | 2023-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-6d2eb34905f7419ca7f3a7451cc9953e2023-09-01T15:50:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-08-0111810.1136/jitc-2023-007118Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3Daniel J DeAngelo0Yi Lin1Roch Houot2Marion Subklewe3Petra C Schuberth4Michael R Bishop5Nicolas Boissel6Dimitrios Tzachanis7Jae H Park8Monique C Minnema9Thibaut Leguay10Mehrdad Abedi11Bijal D Shah12Ryan D Cassaday13Olalekan O Oluwole14Aaron C Logan15Max S Topp16Kristen M O'Dwyer17Martha L Arellano18Maria R Baer19Gary J Schiller20William G Wierda21Patrick J Stiff22Deepa Jeyakumar23Daqin Mao24Sabina Adhikary25Lang Zhou26Rita Damico Khalid27Armin Ghobadia282 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USAAff1 grid.66875.3a000000040459167XMayo Clinic Rochester MN USAAff4 grid.411154.40000000121750984Service d`Hématologie CliniqueCentre Hospitalier Universitaire de Rennes Rennes FranceGerman Cancer Consortium (DKTK), Partner Site Munich, Munich, GermanyAff1 grid.412004.30000000404789977Department of OncologyUniversity Hospital Zurich Zurich SwitzerlandDepartment of Medicine Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, USADépartement d`Hématologie Clinique, Hôpital Saint-Louis, Paris, FranceMoores Cancer Center, UCSD, La Jolla, California, USADepartment of Medicine, Division of Cell Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, USA9 Department of Hematology, UMC Utrecht Cancer Center, Amsterdam, The NetherlandsDepartment of Hematology, Service d`hématologie clinique et thérapie cellulaire Hôpital du Haut-Leveque CHU de Bordeaux, Bordeaux, France6University of California Davis, Sacramento, CA, USADivision of Hematology/Oncology, Department of Malignant Hematology, Moffitt Cancer Center, Tampa, Florida, USAFred Hutchinson Cancer Center, University of Washington, Seattle, Washington, USAVanderbilt-Ingram Cancer Center, Division of Hematology and Oncology, Vanderbilt University, Nashville, Tennessee, USAHelen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USAMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Wurzburg, GermanyWilmot Cancer Institute, University of Rochester, Rochester, New York, USAWinship Cancer Institute, Emory University, Atlanta, Georgia, USAMarlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USADavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Hematology/Oncology, Loyola University Medical Center, Maywood, Illinois, USAChao Comprehensive Cancer Center, University of California Irvine Medical Center, Irvine, California, USAKite, a Gilead Company, Santa Monica, California, USAKite, a Gilead Company, Santa Monica, California, USAKite, a Gilead Company, Santa Monica, California, USAKite, a Gilead Company, Santa Monica, California, USADivision of Medical Oncology, Washington University School of Medicine in Saint Louis, St Louis, Missouri, USABackground Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.Methods Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.Results Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7–58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).Conclusions In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.https://jitc.bmj.com/content/11/8/e007118.full |
| spellingShingle | Daniel J DeAngelo Yi Lin Roch Houot Marion Subklewe Petra C Schuberth Michael R Bishop Nicolas Boissel Dimitrios Tzachanis Jae H Park Monique C Minnema Thibaut Leguay Mehrdad Abedi Bijal D Shah Ryan D Cassaday Olalekan O Oluwole Aaron C Logan Max S Topp Kristen M O'Dwyer Martha L Arellano Maria R Baer Gary J Schiller William G Wierda Patrick J Stiff Deepa Jeyakumar Daqin Mao Sabina Adhikary Lang Zhou Rita Damico Khalid Armin Ghobadia Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 Journal for ImmunoTherapy of Cancer |
| title | Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 |
| title_full | Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 |
| title_fullStr | Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 |
| title_full_unstemmed | Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 |
| title_short | Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3 |
| title_sort | impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory b cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in zuma 3 |
| url | https://jitc.bmj.com/content/11/8/e007118.full |
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