Peripheral blast count at apheresis as a risk factor for survival following tisagenlecleucel in children and young adults
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.
Article Details
Authors (30)
Kaylyn Lyons
1University of Colorado Anschutz Medical Campus, Pediatric Hematology and Oncology, Aurora, United States
Kristen Miller
1University of Colorado Anschutz Medical Campus, Pediatric Hematology and Oncology, Aurora, United States
Arpita Deb
Andrew Nicklawsky
1University of Colorado Anschutz Medical Campus, Pediatric Hematology and Oncology, Aurora, United States
Christina Baggott
Khanh Nguyen
Snehit Prabhu
6Stanford University, Stanford, United States
Holly Pacenta
8Cook Children's Hospital, Fort Worth, United States
Christine Phillips
4Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute, Cincinnati, United States
Jenna Rossoff
1Northwestern University School of Medicine, Chicago, United States
Heather Stefanski
24CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Julie-An Talano
10Medical College of Wisconsin, Milwaukee, United States
Amy Moskop
16Medical College of Wisconsin, Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Milwaukee, United States
Amy Keating
5Dana-Farber/Boston Children's Cancer & Blood Disorders Center, Boston, United States
Susanne Baumeister
17Boston Children's Hospital, Boston, United States
Douglas Myers
11Children's Mercy Hospital, Kansas City, United States
Nicole Karras
1City of Hope, Pediatrics, Duarte, United States
Stacy Cooper
9Johns Hopkins School of Medicine, Department of Oncology, Baltimore, United States
Muna Qayed
Michelle Hermiston
13University of California San Francisco Benioff Children's Hospita, San Francisco, United States
Prakash Satwani
15Columbia University, New York, United States
Christa Krupski
9Cincinnati Children's Hospital, Cincinnati, United States
Vasant Chinnabhandar
15The Univeristy of Western Australia, Pediatrics, Perth, Australia
Crystal Mackall
2Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, CA
Samuel John
Theodore Laetsch
20Children's Hospital of Philadelphia, Philadelphia, United States
Kevin Curran
19Memorial Sloan Kettering, New York, United States
Michael Verneris
1University of Colorado School of Medicine, Aurora, United States
Liora Schultz
Vanessa Fabrizio
6Division of Pediatric Hematology-Oncology-BMT, University of Colorado, Aurora, United States