Disease Burden Affects Outcomes in Pediatric and Young Adult B-ALL After Commercial Tisagenlecleucel: A Pediatric Real-World CAR Consortium

鈥� An ASCO Reading Room selection

November 17, 2022

Liora Schultz, MD; Christina Baggott, PhD; Snehit Prabhu, PhD; Holly Pacenta, MD; Christine Phillips, MD; Jenna Rossoff, MD; Heather Stefanski, MD, PhD; Julie-An Talano, MD; Amy Moskop, MD; Steven Margossian, MD, PhD; Michael Verneris, MD; Gary Douglas Myers, MD; Nicole Karras, MD; Patrick Brown, MD; Muna Qayed, MD, MSc; Michelle Hermiston, MD, PhD; Prakash Satwani, MD; Christa Krupski, DO, MPH; Amy Keating, MD; Rachel Wilcox, BS; Cara Rabik, MD, PhD; Vanessa Fabrizio, MD, MS; Rayne Rouce, MD; Vasant Chinnabhandar, MD; Michael Kunicki, BS; Valentin Barsan, MD; A. Yasemin Goksenin, MD, PhD; Yimei Li, PhD; Sharon Mavroukakis, MS; Emily Egeler, PhD; Kevin Curran, MD; Crystal Mackall, MD; and Theodore Laetsch, MD

Journal of Clinical Oncology

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Purpose

Tisagenlecleucel is a CD19-specific chimeric antigen receptor T-cell therapy, U.S. 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 U.S. 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 U.S. 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 72-84%). The infused cohort had an 85% CR (95% CI 79-89%) and 12-month OS of 72% and EFS of 50%, with 335 days of median 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<0.0001 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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Disease Burden Affects Outcomes in Pediatric and Young Adult B-ALL After Commercial Tisagenlecleucel: A Pediatric Real-World CAR Consortium

Primary Source

Journal of Clinical Oncolog

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