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. 2024 May 15;30(10):2085-2096.
doi: 10.1158/1078-0432.CCR-23-3759.

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

Aina Oliver-Caldes  1   2 , Marta Español-Rego  1 , Aintzane Zabaleta  3 , Verónica González-Calle  4 , Sergio Navarro-Velázquez  1 , Susana Inogés  3 , Ascensión López-Díaz de Cerio  3 , Valentín Cabañas  5 , Nieves López-Muñoz  6 , Paula Rodríguez-Otero  3 , Juan Luis Reguera  7 , David F Moreno  1 , Nuria Martínez-Cibrian  1 , Lucía López-Corral  4 , Lorena Pérez-Amill  1 , Beatriz Martin-Antonio  8 , Laura Rosiñol  1 , Joan Cid  1 , Natalia Tovar  1 , Joaquín Sáez-Peñataro  1 , Miriam López-Parra  4 , Eulalia Olesti  1 , Elena Guillén  1 , Sara Varea  1 , Luis Gerardo Rodríguez-Lobato  1 , Anthony M Battram  1 , Marta Sonia González  9 , Andrés Sánchez-Salinas  5 , Azucena González-Navarro  1 , Valentín Ortiz-Maldonado  1 , Julio Delgado  1 , Felipe Prósper  3 , Manel Juan  1 , Joaquín Martínez-López  6 , José M Moraleda  5 , Maria Victoria Mateos  4 , Álvaro Urbano-Ispizua  1 , Bruno Paiva  3 , Mariona Pascal  1 , Carlos Fernández de Larrea  1
Affiliations
Free article

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

Aina Oliver-Caldes et al. Clin Cancer Res. .
Free article

Abstract

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.

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