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Type of Anti-CD19 CAR-T Infusion Impacts Safety, Efficacy in Patients With LBCL
Clinical study findings suggest that heterogeneity of CAR T-cell infusion products affect the efficacy and toxicity of axicabtagene ciloleucel (axi-cel) therapy in patients with large B cell lymphoma (LBCL; Nat Med. 2020 Oct 5. Epub ahead of print.).
“Autologous [CAR-T therapies] targeting CD19 have high efficacy in [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,” wrote Michael R. Green, MD, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Seeking to identify transcriptomic features of autologous axi-cel anti-CD19 CAR T cell infusion products tied to efficacy and toxicity, Dr Green et al conducted single-cell RNA sequencing with capture-based cell identification in 24 patients with LBCL.
Patients achieving complete responses at their 3-month follow-up determined by positron emission tomography/computed tomography had 3-fold higher frequencies of CD8 T cells expressing memory signatures than did those with partial responses or progressive disease.
Molecular response that was measured 7 days after infusion via cell-free DNA sequencing was significantly associated with clinical response (P = .008), and a signature of CD8 T cell exhaustion was tied to (q = 2.8 × 10−149) poor molecular response.
In addition, a relationship was observed between rare cell population with monocyte-like transcriptional features (P = .0002) and 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,” Dr Green and co-investigators concluded.—Hina M. Porcelli
