CARBIOM will enroll up to 45 participants to obtain 40 reinfused and evaluable participants at Month 1: 20 with B-cell lymphoma and 20 with multiple myeloma. CAR-T treatment and all disease-directed care remain standard of care and are not assigned by the study. Research procedures consist mainly of protocol-specific blood and stool sampling and laboratory analyses.
The primary analysis will longitudinally characterize CAR-positive and CAR-negative T-cell subpopulations, including expansion and decline, activation, differentiation, exhaustion, and T-cell receptor repertoire diversity, clonality and persistence. Analyses will use spectral flow cytometry and sequencing at apheresis, in the CAR-T bag before infusion, at Day 7 +/- 3 days and at Month 1 +/- 7 days. These parameters will be compared according to Month 1 response assessed using Lugano 2014 criteria for B-cell lymphomas or International Myeloma Working Group criteria for multiple myeloma.
Secondary and exploratory analyses will describe Month 3 response; 12-month progression-free survival, overall survival and non-relapse mortality; bridging therapy; CAR-T expansion and persistence by routine flow cytometry and digital PCR; cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and prolonged cytopenias; PET-derived tumour burden; apheresis and CAR-T product features; tumour genomics, clonal haematopoiesis, antibiotic exposure and gut microbiota; and will establish a biobank of frozen cells, RNA and DNA for future ancillary analyses.
