PMID- 37874957 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240108 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 42 IP - 2 DP - 2024 Jan 10 TI - Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy. PG - 205-217 LID - 10.1200/JCO.23.01097 [doi] AB - PURPOSE: Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure. METHODS: The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naive patients. RESULTS: The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3(+) cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naive group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naive patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes. CONCLUSION: Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates. FAU - Iacoboni, Gloria AU - Iacoboni G AUID- ORCID: 0000-0003-0805-9288 AD - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. AD - Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Navarro, Victor AU - Navarro V AUID- ORCID: 0000-0001-6925-4605 AD - Oncology Data Science (ODySey) Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. FAU - Martin-Lopez, Ana Africa AU - Martin-Lopez AA AD - Hematology Department, Hospital Clinico Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain. AD - Centro de Investigacion del Cancer-IBMCC, Salamanca, Spain. FAU - Rejeski, Kai AU - Rejeski K AUID- ORCID: 0000-0003-3905-0251 AD - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. AD - Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany. AD - German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany. FAU - Kwon, Mi AU - Kwon M AUID- ORCID: 0000-0002-3855-7774 AD - Department of Hematology, Hospital General Universitario Gregorio Maranon, Madrid, Spain. AD - Gregorio Maranon Health Research Institute (IiSGM), Madrid, Spain. FAU - Jalowiec, Katarzyna Aleksandra AU - Jalowiec KA AUID- ORCID: 0000-0003-3284-8308 AD - Hematology Department, University College London Cancer Institute, London, United Kingdom. AD - Department of Hematology and Central Hematology Laboratory, University Hospital of Bern, Bern, Switzerland. FAU - Amat, Paula AU - Amat P AD - Haematology Department, Hospital Clinico Universitario, Valencia, Spain. AD - INCLIVA Research Institute, Valencia, Spain. FAU - Reguera-Ortega, Juan Luis AU - Reguera-Ortega JL AD - Hematology Department, Hospital Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain. FAU - Gallur, Laura AU - Gallur L AUID- ORCID: 0000-0001-6293-9281 AD - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. AD - Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Blumenberg, Viktoria AU - Blumenberg V AUID- ORCID: 0000-0003-1379-0876 AD - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. AD - Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany. AD - German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany. FAU - Gutierrez-Herrero, Sara AU - Gutierrez-Herrero S AUID- ORCID: 0000-0001-5507-3985 AD - Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL) and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain. FAU - Roddie, Claire AU - Roddie C AUID- ORCID: 0000-0002-4901-5858 AD - Hematology Department, University College London Cancer Institute, London, United Kingdom. FAU - Benzaquen, Ana AU - Benzaquen A AUID- ORCID: 0000-0003-4015-0831 AD - Haematology Department, Hospital Clinico Universitario, Valencia, Spain. AD - INCLIVA Research Institute, Valencia, Spain. FAU - Delgado-Serrano, Javier AU - Delgado-Serrano J AD - Hematology Department, Hospital Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain. FAU - Sanchez-Salinas, Mario Andres AU - Sanchez-Salinas MA AD - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. AD - Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Bailen, Rebeca AU - Bailen R AD - Department of Hematology, Hospital General Universitario Gregorio Maranon, Madrid, Spain. AD - Gregorio Maranon Health Research Institute (IiSGM), Madrid, Spain. FAU - Carpio, Cecilia AU - Carpio C AD - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. AD - Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Lopez-Corral, Lucia AU - Lopez-Corral L AD - Hematology Department, Hospital Clinico Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain. AD - Centro de Investigacion del Cancer-IBMCC, Salamanca, Spain. FAU - Hernani, Rafael AU - Hernani R AUID- ORCID: 0000-0003-1043-8076 AD - Haematology Department, Hospital Clinico Universitario, Valencia, Spain. AD - INCLIVA Research Institute, Valencia, Spain. FAU - Bastos, Mariana AU - Bastos M AUID- ORCID: 0000-0002-9431-4646 AD - Department of Hematology, Hospital General Universitario Gregorio Maranon, Madrid, Spain. AD - Gregorio Maranon Health Research Institute (IiSGM), Madrid, Spain. FAU - O'Reilly, Maeve AU - O'Reilly M AUID- ORCID: 0000-0002-2702-397X AD - Hematology Department, University College London Cancer Institute, London, United Kingdom. FAU - Martin-Martin, Lourdes AU - Martin-Martin L AUID- ORCID: 0000-0001-7996-570X AD - Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL) and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain. FAU - Subklewe, Marion AU - Subklewe M AUID- ORCID: 0000-0001-5708-1479 AD - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. AD - Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany. AD - German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany. FAU - Barba, Pere AU - Barba P AUID- ORCID: 0000-0001-7076-7969 AD - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. AD - Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. LA - eng PT - Journal Article DEP - 20231024 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Receptors, Chimeric Antigen) RN - 981Y8SX18M (Bendamustine Hydrochloride) RN - 0 (Antigens, CD19) SB - IM MH - Humans MH - *Receptors, Chimeric Antigen MH - Bendamustine Hydrochloride/adverse effects MH - Immunotherapy, Adoptive/adverse effects MH - *Blood Component Removal MH - *Lymphoma, Large B-Cell, Diffuse MH - Antigens, CD19 MH - Cell- and Tissue-Based Therapy EDAT- 2023/10/24 18:42 MHDA- 2024/01/08 06:43 CRDT- 2023/10/24 16:02 PHST- 2024/01/08 06:43 [medline] PHST- 2023/10/24 18:42 [pubmed] PHST- 2023/10/24 16:02 [entrez] AID - 10.1200/JCO.23.01097 [doi] PST - ppublish SO - J Clin Oncol. 2024 Jan 10;42(2):205-217. doi: 10.1200/JCO.23.01097. Epub 2023 Oct 24.