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Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma.
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BackgroundBCMA-CARTs 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.MethodsWe 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.ResultsAt cutoff date March 17th 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%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.ConclusionDespite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.
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OLIVER CALDES, Aina, ESPAÑOL REGO, Marta, ZABALETA, A., GONZÁLEZ CALLE, V., NAVARRO VELÁZQUEZ, Sergio, INOGÉS, S., LOPEZ DIAZ DE CERIO, A., CABAÑAS, V., LÓPEZ MUÑOZ, N., RODRÍGUEZ OTERO, P., REGUERA ORTEGA, J. l., MORENO FAJARDO, David fernando, MARTÍNEZ CIBRIAN, Nuria, LOPEZ CORRAL, L., PEREZ AMILL, Lorena, MARTÍN ANTONIO, Araceli beatriz, ROSIÑOL DACHS, Laura, CID VIDAL, Joan, TOVAR GOMIS, Natalia, SÁEZ PEÑATARO, Joaquín, LÓPEZ PARRA, M., OLESTI MUÑOZ, Eulàlia, GUILLÉN OLMOS, Elena, VAREA LATORRE, Sara, RODRIGUEZ LOBATO, Luis gerardo, BATTRAM, Anthony m., GONZALEZ PEREZ, M. s., SÁNCHEZ SALINAS, A., GONZALEZ NAVARRO, Europa azucena, ORTIZ MALDONADO, Valentín, DELGADO, Julio (delgado gonzález), PROSPER, F., JUAN, Manel, MARTINEZ LOPEZ, J., MORALEDA, J. m., MATEOS, M. v., URBANO ISPIZUA, Álvaro, PAIVA, B., PASCAL CAPDEVILA, Mariona, FERNÁNDEZ DE LARREA RODRÍGUEZ, Carlos josé. Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma.. _Clinical Cancer Research_. 2024. Vol. 30, núm. 10, pàgs. 2085-2096. [consulta: 25 de desembre de 2025]. ISSN: 1557-3265. [Disponible a: https://hdl.handle.net/2445/216862]