Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma. Scientific Publication

Mar 11, 2024 | Magazine: Clinical Cancer Research

Aina Oliver-Caldés 1 , Marta Español-Rego 2 , Aintzane Zabaleta 3 , Veronica Gonzalez-Calle 4 , Sergio Navarro-Velázquez 5 , Susana Inoges 6 , Ascensión López-Díaz de Cerio 7 , Valentin Cabañas 8 , Nieves López-Muñoz 9 , Paula Rodriguez-Otero 10 , Juan Luis Reguera-Ortega 11 , David F Moreno 12 , Núria Martínez-Cibrian 5 , Lucía López-Corral 13 , Lorena Pérez-Amill 14 , Beatriz Martin-Antonio 15 , Laura Rosinol 16 , Joan Cid 17 , Natalia Tovar 18 , Joaquin Saez-Peñataro 12 , Miriam Lopez-Parra 19 , Eulalia Olesti 12 , Elena Guillen 12 , Sara Varea 12 , Luis Gerardo Rodríguez-Lobato 16 , Anthony M Battram 20 , Marta-Sonia Gonzalez-Perez 21 , Andres Sanchez-Salinas 22 , Azucena González-Navarro 23 , Valentin Ortiz-Maldonado 12 , Julio Delgado 24 , Felipe Prosper 10 , Manel Juan 25 , Joaquin Martinez-Lopez 26 , Jose M Moraleda 27 , Maria Victoria Mateos 28 , Alvaro Urbano-Ispizua 1 , Bruno Paiva 29 , Mariona Pascal 5 , Carlos Fernández de Larrea 30

Background: BCMA-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.

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 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.

Conclusion: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.

CITATION Clin Cancer Res. 2024 Mar 11. doi: 10.1158/1078-0432.CCR-23-3759

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