Faculty Collaboration Database

Higher doses of tisagenlecleucel are associated with improved outcomes: a report from the pediatric real-world CAR consortium. Blood Adv 2023 Feb 28;7(4):541-548

Date

08/09/2022

Pubmed ID

35938863

Pubmed Central ID

PMC9979765

DOI

10.1182/bloodadvances.2022007246

Scopus ID

2-s2.0-85139688392 (requires institutional sign-in at Scopus site)   51 Citations

Abstract

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if CAR T-cell dose affects overall survival (OS), event-free survival (EFS), or relapse-free-survival (RFS) in tisagenlecleucel recipients. Retrospective data were collected from Pediatric Real World CAR Consortium member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1.7 × 106 CAR T cells per kg. To assess the impact of cell dose, we divided responders into dose quartiles: 0.134 to 1.300 × 106 (n = 48 [27%]), 1.301 to 1.700 × 106 (n = 46 [26%]), 1.701 to 2.400 × 106 (n = 43 [24%]), and 2.401 to 5.100 × 106 (n = 43 [24%]). OS, EFS, and RFS were improved in patients who received higher doses of tisagenlecleucel (P = .031, .0079, and .0045, respectively). Higher doses of tisagenlecleucel were not associated with increased toxicity. Because the current tisagenlecleucel package insert dose range remains broad, this work has implications in regard to targeting higher cell doses, within the approved dose range, to optimize patients' potential for long-standing remission.

Author List

Stefanski HE, Eaton A, Baggott C, Rossoff J, Verneris MR, Prabhu S, Pacenta HL, Phillips CL, Talano JA, Moskop A, Margossian SP, Myers GD, Karras NA, Brown PA, Qayed M, Hermiston M, Satwani P, Krupski MC, Keating AK, Wilcox R, Rabik CA, Fabrizio VA, Chinnabhandar V, Goksenin AY, Curran KJ, Mackall CL, Laetsch TW, Schultz LM

Authors

Amy Moskop MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Child
Chronic Disease
Humans
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Receptors, Antigen, T-Cell
Recurrence
Retrospective Studies
T-Lymphocytes
United States