DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

作者：Kitsada Wudhikarn, Martina Pennisi, Marta García‐Recio, Jessica Flynn, Aishat Olaide Afuye, Mari Lynne Silverberg, Molly Maloy, Sean M. Devlin, Connie Lee Batlevi, Gunjan L. Shah, Michael Scordo, Maria Lia Palomba, Parastoo B. Dahi, Craig S. Sauter, Bianca Santomasso, Elena Mead, Miguel‐Angel Perales · 发表于：Blood Advances · 年份：2020 · DOI：10.1182/bloodadvances.2020001972 · 被引用次数：141 · 研究领域：CAR-T cell therapy research、Advancements in Semiconductor Devices and Circuit Design、Integrated Circuits and Semiconductor Failure Analysis

Cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell-mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely...