Optimal fludarabine lymphodepletion is associated with improved outcomes after CAR T-cell therapy Journal Article
| Authors: | Fabrizio, V. A.; Boelens, J. J.; Mauguen, A.; Baggott, C.; Prabhu, S.; Egeler, E.; Mavroukakis, S.; Pacenta, H.; Phillips, C. L.; Rossoff, J.; Stefanski, H. E.; Talano, J. A.; Moskop, A.; Margossian, S. P.; Verneris, M. R.; Myers, G. D.; Karras, N. A.; Brown, P. A.; Qayed, M.; Hermiston, M.; Satwani, P.; Krupski, C.; Keating, A. K.; Wilcox, R.; Rabik, C. A.; Chinnabhandar, V.; Kunicki, M.; Goksenin, A. Y.; Mackall, C. L.; Laetsch, T. W.; Schultz, L. M.; Curran, K. J. |
| Article Title: | Optimal fludarabine lymphodepletion is associated with improved outcomes after CAR T-cell therapy |
| Abstract: | Chimeric antigen receptor (CAR) T cells provide a therapeutic option in hematologic malignancies. However, treatment failure after initial response approaches 50%. In allogeneic hematopoietic cell transplantation, optimal fludarabine exposure improves immune reconstitution, resulting in lower nonrelapse mortality and increased survival. We hypothesized that optimal fludarabine exposure in lymphodepleting chemotherapy before CAR T-cell therapy would improve outcomes. In a retrospective analysis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia undergoing CAR T-cell (tisagenlecleucel) infusion after cyclophosphamide/fludarabine lymphodepleting chemotherapy, we estimated fludarabine exposure as area under the curve (AUC; mg × h/L) using a validated population pharmacokinetic (PK) model. Fludarabine exposure was related to overall survival (OS), cumulative incidence of relapse (CIR), and a composite end point (loss of B-cell aplasia [BCA] or relapse). Eligible patients (n 5 152) had a median age of 12.5 years (range, <1 to 26), response rate of 86% (n 5 131 of 152), 12-month OS of 75.1% (95% confidence interval [CI], 67.6% to 82.6%), and 12-month CIR of 36.4% (95% CI, 27.5% to 45.2%). Optimal fludarabine exposure was determined as AUC © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
| Journal Title: | Blood Advances |
| Volume: | 6 |
| Issue: | 7 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2022-04-12 |
| Start Page: | 1961 |
| End Page: | 1968 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2021006418 |
| PUBMED: | 34788386 |
| PROVIDER: | scopus |
| PMCID: | PMC9006295 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 2 May 2022 -- Source: Scopus |
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