Extended Data Fig. 2: CART-associated immune-related adverse events (CirAE) Clinical correlates in the cilta-cel cohort.
(a) Response rate in the cilta-cel cohort stratified by CART-associated immune-related adverse events, CirAE. Categorical variables were compared with Fisher’s exact test. (b) Progression-free survival (PFS) analysis of the cilta-cel cohort, stratified by CirAE. Survival distributions were compared with the log-rank test. (c) Overall survival (OS) analysis of the cilta-cel cohort, stratified by CirAE. Survival distributions were compared with the log-rank test. (d) Non-relapse mortality (NRM) analysis of the cilta-cel cohort, stratified by CirAE. Survival distributions were compared with the log-rank test. (e) Pre-infusion M-spike levels of the cilta-cel cohort, stratified by CirAE. Data are shown as median values with error bars representing the 25th and 75th percentiles. Statistical comparisons between groups were performed using the two-tailed Wilcoxin test. (f) Pre-infusion differential free light chain (dFLC) levels of the cilta-cel cohort, stratified by CirAE. Data are shown as median values with error bars representing the 25th and 75th percentiles. Statistical comparisons between groups were performed using the two-tailed Wilcoxin test. (g) Cytokine release syndrome (CRS) grade of the cilta-cel cohort, stratified by CirAE. Categorical variables were compared with Fisher’s exact test. (h) Immune effector cell-associated neurotoxicity (ICANS) grade of the cilta-cel cohort, stratified by CirAE. Categorical variables were compared with Fisher’s exact test. (i) Top: absolute lymphocyte count (ALC; median with interquartile range) within the 28 days following BCMA-CART, and at Day 28, Month 3 and Month 6, in the cilta-cel cohort, stratified by CirAE. Data are presented as mean values ± 95% confidence interval. Bottom: peak absolute lymphocyte count (ALCPeak) at apheresis, Day 0, Day 7, Day 14, and Day 21 of the cilta-cel cohort, stratified by CirAE (bottom). Data are presented as median values ± interquartile range. Day 14 ALCPeak of 2.9 falls within the third quartile of the cilta-cel non-CirAE cohort distribution. Statistical comparisons between groups were performed using the two-tailed Wilcoxin test. * Indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001. Exact P-values are provided in Supplementary Table S9. (j) Top: CD4+ and CD8+ proportion of T-cells in the cilta-cel cohort, stratified by CirAE. Bar graphs show the median and the error bars denote the 25th and 75th percentiles. Bottom: area under the curve (AUC) analysis of CD4⁺ T-cell proportions from apheresis to Month 6 in the cilta-cel cohort, stratified by CirAE. Data are shown as median values with error bars representing the 25th and 75th percentiles. Statistical comparisons between groups were performed using the two-tailed Wilcoxin test. Exact P-values are provided in Supplementary Table S9. (k) Univariable logistic regression was performed using a binomial generalized linear model to assess associations between clinical factors and CirAE (left), neurologic CirAE (neuro-CirAE, middle), and non-neuro CirAE (right). Statistical significance of model coefficients was assessed using two-tailed Wald tests. (l) Multivariable logistic regression analysis of risk factors for CirAE development in the cilta-cel cohort. Statistical significance of model coefficients was assessed using two-tailed Wald tests. ALCPeak: peak absolute lymphocyte count; AUC: area under curve; CART: CAR T-cell; cilta-cel: ciltacabtagene-autoleucel; CI: confidence interval; CirAE: CART-associated immune-related adverse events; CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity syndrome; NRM: non-relapse mortality; ORR: overall response rate; OS: overall survival; ide-cel: idacabtagene-vicleucel; PFS: progression free survival; ≥ VGPR: very good partial response or better.
