468 Classification of patients who do not develop early CRS/ICANS in relapsed/refractory large B-cell lymphoma using ZUMA clinical trial data
Year: 2024
Type: conference-abstract
Abstract: Background As the use of CAR T-cell therapy expands for the treatment of relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) given its proven long-term efficacy, there has been increasing community interest in exploring outpatient administration. One of the consensus recommendations for successful implementation of an outpatient program includes the development of actionable and feasible prospective models to estimate toxicity risk to assist providers with patient management.1 Methods We conducted an observational, retrospective cohort study using secondary data from 390 patients treated with the CD19 CAR T-cell therapy axicabtagene ciloleucel (axi-cel) under two prospective, institutional review board-approved clinical trials, ZUMA-1 (NCT02348216)2–4 and ZUMA-7 (NCT03391466)5; these clinical trials enrolled consenting adult patients with R/R LBCL between 2015 and 2019. Using machine learning and statistical methods, we developed a multivariable classification model for identifying patients unlikely to experience early cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade using a set of 50 actionable and feasible markers (i.e., demographics, disease characteristics, and routine clinical labs collected before the start of lymphodepletion). The model was developed in an 80% development cohort and evaluated in the remaining 20% holdout validation cohort. Top models were identified as those having high area under the receiver operating characteristic curve (AUROC) and high positive predictive value (PPV). Results We found the use of prophylactic corticosteroids to be an important factor in remaining CRS- and ICANS-free within the first three days post-treatment (p<0.001). We identified a top model for no early CRS/ICANS using a set of 6 pre-treatment features: (fewer) number of lines of prior systemic therapy, (younger) age, (lower) baseline tumor burden (as measured by sum of the product of the diameters), (lower) C-reactive protein, (lower) aspartate transaminase (AST), and (higher) hemoglobin. Our top model achieved a PPV of 0.84 and 0.71 in the development and validation cohorts, respectively. Furthermore, we observed that our top model also had a strong inverse association with incidence of higher grade ICANS (p<0.001). The addition of pre-treatment cytokine and chemokine markers, e.g., IL-6, IL-7, and MDC, was observed to improve the performance of our top model by several percentage points. Conclusions We illustrated that routine clinical variables can be used to identify axi-cel-treated R/R LBCL patients at low risk of developing early post-treatment CRS and/or ICANS. Such knowledge can be used to help treating centers prospectively manage patient care, including consideration of outpatient treatment. References Oluwole OO, Dholaria B, Knight TE, Jain T, Locke FL, Ramsdell L, et al. Chimeric antigen receptor T-cell therapy in the outpatient setting: an expert panel opinion from the American Society for Transplantation and cellular therapy. Transplant Cell Ther. 2024;30(2):131–42. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44. Topp MS, Meerten TM, Houot R, Minnema MC, Bouabdallah K, Lugtenburg PJ, et al. Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021;195(3):388–98. Oluwole OO, Bouabdallah K, Munoz J, De Guibert S, Vose JM, Bartlett NL, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021. Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–54.
Authors: Kelly Speth, Mike Mattie, Jenny Kim, Jin Xie, Rhine Shen, Jorge Andrade, Qinghua Song, Davide Bedognetti, Sabina Adhikary
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404065629