2026-04-17T14:55:59Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/128362025-05-03T03:19:26Zcom_2072_378070com_2072_378040col_2072_378092

Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas Chong, Elise A. Penuel, Elicia Napier, Ellen Lundberg, Rachel K. Shadman, Mazyar Budde, Lihua Bosch, Francesc Institut Català de la Salut [Chong EA, Napier EB, Lundberg RK] Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA. [Penuel E] Genentech, Inc, South San Francisco, USA. [Budde LE] Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, USA. [Shadman M] Clinical Research Division, Fred Hutchinson Cancer Center and Hematology and Medical Oncology Division, University of Washington, Seattle, USA. [Bosch F] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Cèl·lules B - Tumors - Immunoteràpia Limfomes - Immunoteràpia Anticossos monoclonals - Ús terapèutic DISEASES::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades linfáticas::trastornos linfoproliferativos::linfoma::linfoma no Hodgkin::linfoma de células B Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados Impact of CAR T-cell therapy; Efficacy; Refractory B-cell lymphomas Teràpia de cèl·lules T CAR; Eficàcia; Limfomes de cèl·lules B refractaris Terapia de células T CAR; Eficacia; Linfomas de células B refractarios Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)–modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = .006, unadjusted for multiple comparisons). Most patients (20/30) did not receive intervening therapy between CAR-T administration and mosunetuzumab. The remainder of patients received 1 intervening therapy after a protocol-mandated drug washout. After mosunetuzumab, responding patients had higher lymphocytes (995 vs 400 cells per μL; P = .02) and greater increases in CD4 and CD8 cells (median change, 73 vs –90 cells per μL [P = .005] and 243 vs –103 cells per μL [P = .004], respectively). Additionally, responding patients had an increase in activated CD8 cells (median fold change, 1.7; P = .02). Nonresponders had a relative decrease in CAR transgene levels (n = 16; P = .04). This is, to our knowledge, the first study to assess changes in lymphocytes, T cells, and CAR transgene levels in patients treated with BsAbs after CAR-T. These findings suggest an interaction between prior CAR-T and BsAb outcomes and have implications for optimal timing of BsAb after CAR-T. The trial was registered at www.ClinicalTrials.gov as #NCT02500407. 2025-03-26T13:22:50Z 2025-03-26T13:22:50Z 2025-02-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Chong EA, Penuel E, Napier EB, Lundberg RK, Budde LE, Shadman M, et al. Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas. Blood Adv. 2025 Feb 12;9(4):696–703. 2473-9537 http://hdl.handle.net/11351/12836 10.1182/bloodadvances.2024013640 39571171 001444483800001 http://hdl.handle.net/11351/12836 eng Blood Advances;9(4) https://doi.org/10.1182/bloodadvances.2024013640 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf American Society of Hematology Scientia