Preapheresis clinical patient profiles predict patient’s manufacturing fitness and efficacy with idecabtagene vicleucel

Interplay between baseline clinical factors, apheresis material, manufacturing performance, and clinical outcomes in patients with relapsed/refractory multiple myeloma treated with idecabtagene vicleucel (ide-cel) remains poorly defined. We performed unsupervised clustering of manufacturing data from 164 clinical trial participants to identify distinct manufacturing profiles. Clinical variables and outcomes were not included in cluster generation. After cluster identification, we conducted post hoc analysis of manufacturing features to characterize each cluster biologically and subsequent univariate comparisons with clinical characteristics and treatment outcomes, which had not informed the initial clustering process. Cluster 1, the least favorable manufacturing profile, was characterized by lower transduction efficiency, delayed activation (smaller day 5 cell size), reduced vector copy number, decreased potency in vitro, and more than threefold lower final cell yield. Cluster 1 patients exhibited higher baseline tumor burden, lower albumin, and lower lymphocyte counts before apheresis ( P < .05). This unfavorable profile was associated with impaired chimeric antigen receptor T-cell expansion, lower complete response rates (18% vs 41%; P = .1), and shorter progression-free survival (2.9 vs 10 months; P = .0019). Mapping these features in 109 real-world ide-cel recipients confirmed these findings. Our results highlight the critical influence of baseline disease burden, inflammation, and immune health, on manufacturing success and patient outcomes.