Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.

Autor:	Oliver-Caldes A; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.; Hospital Universitari Son Espases, IDISBA, Palma de Mallorca, Spain., Español-Rego M; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Zabaleta A; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., González-Calle V; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain., Navarro-Velázquez S; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Inogés S; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., de Cerio AL; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., Cabañas V; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia, Spain., López-Muñoz N; Hospital Universitario 12 de Octubre, Complutense University, i+12, CNIO, Madrid, Spain., Rodríguez-Otero P; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., Reguera JL; Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), University of Sevilla, Sevilla, Spain., Moreno DF; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Martínez-Cibrian N; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., López-Corral L; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain., Pérez-Amill L; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Martin-Antonio B; Department of Experimental Hematology, Instituto de Investigación Sanitaria- Fundación Jiménez Díaz, University Autonomous of Madrid, Madrid, Spain., Rosiñol L; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Cid J; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Tovar N; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Sáez-Peñataro J; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., López-Parra M; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain., Olesti E; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Guillén E; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Varea S; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Rodríguez-Lobato LG; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Battram AM; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., González MS; Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain., Sánchez-Salinas A; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia, Spain., González-Navarro A; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Ortiz-Maldonado V; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Delgado J; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Prósper F; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., Juan M; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Martínez-López J; Hospital Universitario 12 de Octubre, Complutense University, i+12, CNIO, Madrid, Spain., Moraleda JM; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia, Spain., Mateos MV; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain., Urbano-Ispizua Á; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Paiva B; Clínica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBER-ONC Number CB16/12/00369, Pamplona, Spain., Pascal M; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain., Fernández de Larrea C; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 May 15; Vol. 30 (10), pp. 2085-2096.
DOI:	10.1158/1078-0432.CCR-23-3759
Abstrakt:	Purpose: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial. Patients and Methods: We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes. Results: At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2-37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5-100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5-22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse. Conclusions: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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