Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: A pediatric real-world chimeric antigen receptor consortium report Journal Article
| Authors: | Schultz, L. M.; Baggott, C.; Prabhu, S.; Pacenta, H. L.; 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.; Fabrizio, V. A.; Rouce, R. H.; Chinnabhandar, V.; Kunicki, M.; Barsan, V. V.; Yasemin Goksenin, A.; Li, Y.; Mavroukakis, S.; Egeler, E.; Curran, K. J.; Mackall, C. L.; Laetsch, T. W. |
| Article Title: | Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: A pediatric real-world chimeric antigen receptor consortium report |
| Abstract: | PURPOSE Tisagenlecleucel is a CD19-specific chimeric antigen receptor T-cell therapy, US Food and Drug Administration-approved for children, adolescents, and young adults (CAYA) with relapsed and/or refractory (RR) B-cell acute lymphoblastic leukemia (B-ALL). The US Food and Drug Administration registration for tisagenlecleucel was based on a complete response (CR) rate of 81%, 12-month overall survival (OS) of 76%, and event-free survival (EFS) of 50%. We report clinical outcomes and analyze covariates of outcomes after commercial tisagenlecleucel. METHODS We conducted a retrospective, multi-institutional study of CAYA with RR B-ALL across 15 US institutions, who underwent leukapheresis shipment to Novartis for commercial tisagenlecleucel. A total of 200 patients were included in an intent-to-treat response analysis, and 185 infused patients were analyzed for survival and toxicity. RESULTS Intent-to-treat analysis demonstrates a 79%morphologic CR rate (95%CI, 72 to 84). The infused cohort had an 85%CR (95%CI, 79 to 89) and 12-month OS of 72%and EFS of 50%, with 335 days ofmedian follow-up. Notably, 48% of patients had low-disease burden (<5% bone marrow lymphoblasts, no CNS3, or other extramedullary disease), or undetectable disease, pretisagenlecleucel. Univariate and multivariate analyses associate high-disease burden (HB,≥5% bone marrow lymphoblasts, CNS3, or non-CNS extramedullary) with inferior outcomes, with a 12-month OS of 58%and EFS of 31%compared with low-disease burden (OS; 85%, EFS; 70%) and undetectable disease (OS; 95%, EFS; 72%; P < .0001 for OS and EFS). Grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 21% and 7% overall and 35% and 9% in patients with HB, respectively. CONCLUSION Commercial tisagenlecleucel in CAYA RR B-ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies HB preinfusion to associate with inferior OS and EFS and increased toxicity. © 2022 American Society of Clinical Oncology. All rights reserved. |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 40 |
| Issue: | 9 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2022-03-20 |
| Start Page: | 945 |
| End Page: | 955 |
| Language: | English |
| DOI: | 10.1200/jco.20.03585 |
| PUBMED: | 34882493 |
| PROVIDER: | scopus |
| PMCID: | PMC9384925 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 1 April 2022 -- Source: Scopus |
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