Single center experience of using Anakinra prophylactically at Day 0 to reduce CD19 CART toxicities.
Authors: Nain Priyanshu , Singh Rishabh , Yerraguntla Sandeep , Branham Zachery , Kubiak Michal J , Dalgetty Mark , Pavkov Isabela , Dontu Sruthi , Mian Mohammad , Chauhan Ayushi , Keruakous Amany R. , Bryan Locke Johnson , Jillella Anand P. , Kota Vamsi 
Published: June 2023

e19503

Background: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is an effective line of the treatment for relapsed/refractory CD19 B cell cancers, however navigating Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity (ICANS) still remains a challenging task. Corticosteroids and Tocilizumab are currently the mainstay treatment for toxicities but Anakinra, an IL-1 receptor antagonist has also been successfully used to treat patients receiving CART who develop CRS/ICANS. In this study we set out to describe the utility of prophylactic use of Anakinra in patients receiving CART. Methods: We conducted a single center retrospective analysis of patients who received Anakinra for CRS and ICANS prophylaxis per institutional protocol. Patient data including demographics, cancer history, CRS & ICANS American Society for Transplantation and Cellular Therapy Grades, toxicity treatment history and outcomes during their hospitalization were extracted from our medical records. Institutional review board approval was obtained for this review. Results: A total of 19 patients {Diffuse Large B Cell Lymphoma = 10, Follicular = 2,Mantle cell = 2 and Acute Lymphoblastic Leukemia (ALL) = 5} were enrolled in our cohort. The median age of the patients at the time of T cell infusion was 63 years (range, 26-75). CD19 CAR products included Axicabtagene ciloleucel (8 pts; 42.1%), Brexucabtagene autoleucel (6 pts; 31.5%) and Tisagenlecleucel (5 pts; 26.3%). CRS of all grades was observed in 13 patients (68.4%) with severe CRS (grade 3-4) observed in 1 patient (5.2%) (grade 4;12 days). Median CRS duration was 3 days (range, 1-18). Median max CRS grade was observed for 2 days (range, 1-12). Median time to CRS was 5 days (range; 1-8). ICANS of all grades was observed in 12 patients (63.1%), with severe ICANS (grade3-4) in 5 patients (26.3%) {1 patient with grade 4 for 12 days; 4 patients with grade 3 for a median of 2 days (range;1-4)}. Median time to ICANS was 6 days (range, 1-11). Tocilizumab and corticosteroids were used in 9 patients (47.3%) and 11 patients (57.8%), respectively. Median starting day of Tocilizumab and steroid was on day 4(range, 1-6) and day4 (range, 1-21) respectively. Median dose of Tocilizumab was 2 (range, 1-3). Median dose of total Dexamethasone and Methylprednisolone use was 125mg (range, 10-276) and 3.92 g (range, 3-7.4) respectively for a median of 6 cumulative days (range, 1-22). Three patients (15.7%) required ICU transfer with a median stay of 5 days (range, 4-16). 1 patient died of Neurotoxicity on Day 27(Mantle cell) and 2 ALL patients died due to progression after discharge on Day61 and 256. Conclusions: We observed that prophylactically starting Anakinra at Day 0 appeared to improve CRS and ICANS toxicities in patients receiving CART. Further prospective investigations with larger population pools would be required to better understand its role in CAR T toxicity suppression.