655 Concordance between healthcare providers and expert consensus recommendations in the management, monitoring, and mitigation of adverse events associated with CAR T-cell therapy: an updated analysis

Abstract

BackgroundChimeric antigen receptor (CAR) T-cell therapy has been a major innovative breakthrough for hematologic malignancies. These therapies are associated with unique and potentially serious toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity (ICANS), that require vigilance, prompt recognition, and appropriate management to ensure patient safety and optimal therapeutic benefit. We developed an online tool to give healthcare providers (HCPs) case-specific, evidence-based expert guidance on the management of adverse events (AEs) from CAR T-cell therapy. Here, we report an updated analysis comparing CAR T-cell toxicity management among HCPs using the tool vs the expert consensus recommendations.1MethodsIn March 2019, 5 experts provided consensus guidance for the screening, prophylaxis, monitoring, and management of CRS and ICANS in patients considering or receiving CAR T-cell therapy. This information was used to build the interactive online tool. To use this tool, HCPs enter the AE of interest, the severity of the event,2 and their planned management approach. The HCPs were then shown the expert recommendation for that specific scenario. After viewing the expert recommendation, HCPs were asked if it affected their intended approach.ResultsBetween May 2019 and July 2020, 282 HCPs entered 431 unique case scenarios into the tool. Of the entered cases, 56% were HCPs seeking expert recommendations on pretreatment screening and prophylaxis/monitoring strategies for patients not yet experiencing an AE. Of 188 cases entered for patients who received CAR T-cell therapy and experienced an AE, 67% were CRS and 33% were neurotoxicity/ICANS. Overall the planned toxicity management strategy of HCPs matched the expert recommendations in 57% of cases, with a similar rate of concordance for both CRS and ICANS events. There was no significant difference in concordance rates with expert recommendations by toxicity severity (figure 1) nor among HCPs who indicated they practiced at authorized centers vs those who did not (P = 0.7184). Among HCPs who answered the optional survey on the impact of the tool on their management plan, 30% indicated that the expert recommendations changed their approach.Abstract 655 Figure 1Planned management of HCPs compared with expert recommendations, by gradeConclusionsThese data suggest that many HCPs are challenged to optimally manage CAR T-cell therapy toxicities in concordance with expert recommendations. Use of an online tool providing easy access to evidence-based consensus expert recommendations may improve care and safety in patients treated with CAR T-cell therapy. A detailed analysis of the tool including planned management vs expert recommendations for each toxicity and grade will be presented.ReferencesFrigault MJ, Cartwright M, Marcello K, Quill T, DeAngelo DJ, Galinsky IA, Paul S, Park JH. Management of CAR T-Cell toxicities: concordance and divergence between healthcare providers and expert recommendations. Blood 2019:134:2199.Lee DW, Santomasso BD, Lock FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019;25:625–638.