TY - JOUR
T1 - Disease Burden Affects Outcomes in Pediatric and Young Adult B-Cell Lymphoblastic Leukemia After Commercial Tisagenlecleucel
T2 - A Pediatric Real-World Chimeric Antigen Receptor Consortium Report
AU - Schultz, Liora M.
AU - Baggott, Christina
AU - Prabhu, Snehit
AU - Pacenta, Holly L.
AU - Phillips, Christine L.
AU - Rossoff, Jenna
AU - Stefanski, Heather E.
AU - Talano, Julie An
AU - Moskop, Amy
AU - Margossian, Steven P.
AU - Verneris, Michael R.
AU - Myers, Gary Douglas
AU - Karras, Nicole A.
AU - Brown, Patrick A.
AU - Qayed, Muna
AU - Hermiston, Michelle
AU - Satwani, Prakash
AU - Krupski, Christa
AU - Keating, Amy K.
AU - Wilcox, Rachel
AU - Rabik, Cara A.
AU - Fabrizio, Vanessa A.
AU - Rouce, Rayne H.
AU - Chinnabhandar, Vasant
AU - Kunicki, Michael
AU - Barsan, Valentin V.
AU - Yasemin Goksenin, A.
AU - Li, Yimei
AU - Mavroukakis, Sharon
AU - Egeler, Emily
AU - Curran, Kevin J.
AU - Mackall, Crystal L.
AU - Laetsch, Theodore W.
N1 - Publisher Copyright:
© 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2022/3/20
Y1 - 2022/3/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.20.03585
DO - 10.1200/JCO.20.03585
M3 - Article
C2 - 34882493
AN - SCOPUS:85126005350
SN - 0732-183X
VL - 40
SP - 945
EP - 955
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -