Peripheral blast count at apheresis as a risk factor for survival following tisagenlecleucel in children and young adults

Abstract Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Relapsed or refractory (R/R) B-ALL carries a dismal prognosis.1-3 CD19-specific CAR T cell therapy has emerged as a promising treatment, yet relapse rates among responders remain high, with 40-50% relapsing post-therapy (4-12). This underscores the need for improved strategies to predict and prevent relapse following CAR T cell therapy. This study reports the impact of peripheral blasts at the time of apheresis on outcomes in pediatric and young adult patients with R/R B-ALL treated with CD19-specific CAR T cell therapy. A multi-institutional cohort of 162 patients from the Pediatric Real-World CAR Consortium was retrospectively analyzed. Key outcomes such as day 28 response, event-free survival (EFS), and overall survival (OS) were evaluated based on the presence versus absence of peripheral blasts at apheresis. While response at day 28 was comparable among peripheral blast groups in this cohort, the presence of peripheral blasts at apheresis was associated with inferior EFS (27% vs. 55% at 12 months) and OS (55% vs. 78% at 12 months). However, this association was confounded by disease burden at the time of infusion. In multivariable analysis, higher blast percentage at apheresis was not associated with an increased hazard of death (HR = 1.11, 95% CI: 0.93 - 1.33, p = 0.25). These findings suggest that the association between peripheral blasts at apheresis and inferior survival is largely influenced by disease burden at infusion, highlighting the need for further investigation into the biological and clinical significance of peripheral blasts during CAR T cell manufacturing.

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Publication Details

Journal
Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-7638
Primary Topic
CAR-T cell therapy research
Type
article
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article

Peripheral blast count at apheresis as a risk factor for survival following tisagenlecleucel in children and young adults

Michelle L. Hermiston, Holly Pacenta, Vasant Chinnabhandar, Michael R. Verneris et al.
Blood
CAR-T cell therapy research
article

Peripheral blast count at apheresis as a risk factor for survival following tisagenlecleucel in children and young adults

Michelle L. Hermiston, Holly Pacenta, Vasant Chinnabhandar, Michael R. Verneris, Christa Krupski, Samuel John, Kent Lyons, Vanessa A. Fabrizio, Muna Qayed, Christine Phillips, Arpita Deb, Prakash Satwani, Christina Baggott, Andrew Nicklawsky, Heather E. Stefanski, Stacy Cooper, Kevin J. Curran, Amy K. Keating, Liora M. Schultz, Susanne H.C. Baumeister, Kristen Miller, Khanh Cong Nguyen, Snehit Prabhu, Jenna Rossoff, Nicole Karras, Amy Moskop, Julie‐An Talano, Theodore Willis Laetsch, Crystal L. Mackall, Douglas J. Myers
article en

Abstract

Abstract Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Relapsed or refractory (R/R) B-ALL carries a dismal prognosis.1-3 CD19-specific CAR T cell therapy has emerged as a promising treatment, yet relapse rates among responders remain high, with 40-50% relapsing post-therapy (4-12). This underscores the need for improved strategies to predict and prevent relapse following CAR T cell therapy. This study reports the impact of peripheral blasts at the time of apheresis on outcomes in pediatric and young adult patients with R/R B-ALL treated with CD19-specific CAR T cell therapy. A multi-institutional cohort of 162 patients from the Pediatric Real-World CAR Consortium was retrospectively analyzed. Key outcomes such as day 28 response, event-free survival (EFS), and overall survival (OS) were evaluated based on the presence versus absence of peripheral blasts at apheresis. While response at day 28 was comparable among peripheral blast groups in this cohort, the presence of peripheral blasts at apheresis was associated with inferior EFS (27% vs. 55% at 12 months) and OS (55% vs. 78% at 12 months). However, this association was confounded by disease burden at the time of infusion. In multivariable analysis, higher blast percentage at apheresis was not associated with an increased hazard of death (HR = 1.11, 95% CI: 0.93 - 1.33, p = 0.25). These findings suggest that the association between peripheral blasts at apheresis and inferior survival is largely influenced by disease burden at infusion, highlighting the need for further investigation into the biological and clinical significance of peripheral blasts during CAR T cell manufacturing.

BloodVol. 146(Supplement 1)
City Of Hope National Medical Center (US), National Marrow Donor Program (US), Cancer Prevention Institute of California (US), The University of Western Australia (AU), Medical College of Wisconsin (US), Columbia University Irving Medical Center (US), Kettering University (US), Sidney Kimmel Cancer Center (US), Lurie Children's Hospital (US), UCSF Benioff Children's Hospital (US), Stanford Medicine (US), Children's Healthcare of Atlanta (US), Sidney Kimmel Comprehensive Cancer Center (US), Mercy Hospital (US), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), University of Colorado Anschutz Medical Campus (US), University of Cincinnati (US), University of Pennsylvania (US), The University of Texas Southwestern Medical Center (US), Stanford University (US)
Openalex Percentile: Top 47%
CAR-T cell therapy research
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