A mixed method analysis of toxicities of anti-CD19-CAR T cell therapy in hematological malignancies.

Abstract

e19068 Background: CAR (Chimeric Antigen Receptor) T cell therapy is a promising therapy with significant benefits. But cytokine release syndrome (CRS) and neurological toxicities (NT) are major obstacles in its success. In this study we did mixed method analysis of literature to explore side effect profile of Anti CD19-CAR T cell therapy in hematological malignancies. Methods: A review of literature was done to find appropriate studies on Medline database. Total 11 studies were selected on the basis of 1) Anti CD19-CAR T cell therapy 2) Lymphodepletion 3) Sample size equal to or more than 15, 4) Hematological Malignancies 5) Detailed toxicities mentioned. Data was extremely heterogenous for metanalysis therefore results were descriptively formatted using summary texts and tables. Results: Total patient count was 452, out of them 59% had ALL, 35.61% had NHL and 5.30% had CLL. Majority of studies used second generation CAR T cells (n = 10, 90.1). CAR T cell dosage protocol was variable among studies and it range from 1 X 105 to 1 X 107 cells. CRS occurred in 82.7%, with grade 1-2 CRS in 58.4% and grade 3-4 CRS in 24.3%. CRS presented early (range of median = 2.5 – 4 days) and recovers completely generally with in 1st week (range of median = 4.8 - 8 days). NT are seen in 45.6%, with grade 1-2 NT in 20.6% and grade 3-4 NT in 25.0%. NT have variable presentations, encephalopathy was seen in 22.65% of patients and 3.22% had seizures. For management of side effects 28.6% patients required ICU level of care and 21.86% required pressor support. Tocilizumab was used in 30.7%. Total 10 patients (2.2%) died due to side effects and out of them 6 (1.32%) due to CRS and 4 (0.88%) due to NT. Clinically significant associations were shown between tumor grade and CRS (n = 6, 54.5%), IL-6 and CRS (n = 8, 72.7%), CRP (C reactive Protein) and CRS (n =6, 54.5%), and CRS and NT (n = 7, 63.6%) (Table). Conclusions: This study concludes that CRS and NT are most common side effects of CAR T cell therapy. Most of the time they are completely reversible and manageable with tocilizumab and steroid therapy. Levels of IL6, Interferon gamma, CRP and ferritin are elevated in CRS patients. Therefore, can be used as biomarkers. NT and CRS are also associated with each other and likely share the pathological pathway. [Table: see text]