Severe CRS and Hematologic Toxicity After CAR T-Cell Therapy

Juluri KR, Wu V, Voutsinas JM, et al. Severe Cytokine Release Syndrome Is Associated with Hematologic Toxicity Following CD19 CAR T-Cell Therapy. Blood Advances. 2021; (doi: 10.1182/bloodadvances.2020004142).

New research suggests that hematopoietic recovery in patients following CD19-targeted chimeric antigen receptor (CAR) T-cell therapy could be enhanced by patient selection and improved cytokine release syndrome (CRS) management. The retrospective analysis involved 173 patients who underwent defined-composition CD19 CAR T-cell therapy in a Phase I/II clinical study. The primary endpoints were absolute neutrophil count and platelet count at 28 days post-CAR T-cell infusion. At that point, neutrophil and platelet recovery was 81% and 75% cumulative incidences, respectively. At last follow-up, 9% of the patients had experienced persistent neutropenia and 14% had thrombocytopenia. Debiased LASSO regression analysis revealed higher CRS severity as an independent predictor for lower platelet count and lower pre-lymphodepletion platelet count as independent predictors for lower neutrophil and platelet counts post-CD19 CAR T-cell infusion. Multivariable models including CRS-related cytokines linked higher peak serum levels of interleukin 6 with lower 28th day counts. Conversely, transforming growth factor beta concentrations correlated with higher Day 28 counts.

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