Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas

Q Deng, G Han, N Puebla-Osorio, MCJ Ma, P Strati… - Nature medicine, 2020 - nature.com
Q Deng, G Han, N Puebla-Osorio, MCJ Ma, P Strati, B Chasen, E Dai, M Dang, N Jain…
Nature medicine, 2020nature.com
Autologous chimeric antigen receptor (CAR) T cell therapies targeting CD19 have high
efficacy in large B cell lymphomas (LBCLs), but long-term remissions are observed in less
than half of patients, and treatment-associated adverse events, such as immune effector cell-
associated neurotoxicity syndrome (ICANS), are a clinical challenge. We performed single-
cell RNA sequencing with capture-based cell identification on autologous axicabtagene
ciloleucel (axi-cel) anti-CD19 CAR T cell infusion products to identify transcriptomic features …
Abstract
Autologous chimeric antigen receptor (CAR) T cell therapies targeting CD19 have high efficacy in large B cell lymphomas (LBCLs), but long-term remissions are observed in less than half of patients, and treatment-associated adverse events, such as immune effector cell-associated neurotoxicity syndrome (ICANS), are a clinical challenge. We performed single-cell RNA sequencing with capture-based cell identification on autologous axicabtagene ciloleucel (axi-cel) anti-CD19 CAR T cell infusion products to identify transcriptomic features associated with efficacy and toxicity in 24 patients with LBCL. Patients who achieved a complete response by positron emission tomography/computed tomography at their 3-month follow-up had three-fold higher frequencies of CD8 T cells expressing memory signatures than patients with partial response or progressive disease. Molecular response measured by cell-free DNA sequencing at day 7 after infusion was significantly associated with clinical response (P = 0.008), and a signature of CD8 T cell exhaustion was associated (q = 2.8 × 10−149) with a poor molecular response. Furthermore, a rare cell population with monocyte-like transcriptional features was associated (P = 0.0002) with high-grade ICANS. Our results suggest that heterogeneity in the cellular and molecular features of CAR T cell infusion products contributes to variation in efficacy and toxicity after axi-cel therapy in LBCL, and that day 7 molecular response might serve as an early predictor of CAR T cell efficacy.
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