Tisagenlecleucel outcomes in relapsed/refractory extramedullary ALL: a Pediatric Real World CAR Consortium Report

• Type of Material: Article
• Authors: Vanessa A Fabrizio, University of Colorado, Aurora; Christine L Phillips, University of Cincinnati; Adam Lane, University of Cincinnati; Christina Baggott, Stanford University; Snehit Prabhu, Stanford University; Emily Egeler, Stanford University; Sharon Mavroukakis, Stanford University; Holly Pacenta, The University of Texas Southwestern Medical Center/Children’s Health; Jenna Rossoff, Ann & Robert H. Lurie Children’s Hospital of Chicago; Heather E Stefanski, University of Minnesota, Minneapolis; Julie-An Talano, Medical College of Wisconsin; Amy Moskop, Medical College of Wisconsin; Steven P Margossian, Harvard Medical School; Michael R Verneris, University of Colorado; Gary Douglas Myers, Childrens Mercy Hospital; Nicole A Karras, City of Hope National Medical Center; Patrick A Brown, John Hopkins School of Medicine; Muna Qayed, Emory University; Michelle Hermiston, University of California San Francisco; Prakash Satwani, Columbia University; Christa Krupski, University of Cincinnati; Amy K Keating, University of Colorado; Rachel Wilcox, Children’s Mercy Hospital; Cara A Rabik, Johns Hopkins School of Medicine; Vasant Chinnabhandar, University of Minnesota Minneapolis; Michael Kunicki, Stanford University; Yasemin Goksenin, University of California San Francisco; Kevin J Curran, Mem Sloan Kettering Canc Ctr; Crystal L Mackall, Stanford Cancer Institute; Theodore W Laetsch, University of Texas Southwestern Medical Center/Children’s Health; Liora M Schultz, Stanford University
• Language: English
• Date: 2022-01-25
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021005564
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 6
• Issue: 2
• Start Page: 600
• End Page: 610
• Keywords: SURVIVAL; CHEMOTHERAPY; T-CELL THERAPY; Hematology; CHILDRENS ONCOLOGY GROUP; Science & Technology; ACUTE LYMPHOBLASTIC-LEUKEMIA; RELAPSE; Life Sciences & Biomedicine; REMISSION; TRANSPLANTATION; ADOLESCENTS

Abstract

Chimeric antigen receptor (CAR) T cells have transformed the therapeutic options for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia. Data for CAR therapy in extramedullary (EM) involvement are limited. Retrospective data were abstracted from the Pediatric Real World CAR Consortium (PRWCC) of 184 infused patients from 15 US institutions. Response (complete response) rate, overall survival (OS), relapse-free survival (RFS), and duration of B-cell aplasia (BCA) in patients referred for tisagenlecleucel with EM disease (both central nervous system (CNS)3 and non-CNS EM) were compared with bone marrow (BM) only. Patients with CNS disease were further stratified for comparison. Outcomes are reported on 55 patients with EM disease before CAR therapy (CNS3, n = 40; non- CNS EM, n = 15). The median age at infusion in the CNS cohort was 10 years (range, ,1-25 years), and in the non-CNS EM cohort it was 13 years (range, 2-26 years). In patients with CNS disease, 88% (35 of 40) achieved a complete response vs only 66% (10 of 15) with non- CNS EM disease. Patients with CNS disease (both with and without BM involvement) had 24-month OS outcomes comparable to those of non-CNS EM or BM only (P = .41). There was no difference in 12-month RFS between CNS, non-CNS EM, or BM-only patients (P = .92). No increased toxicity was seen with CNS or non-CNS EM disease (P = .3). Active CNS disease at time of infusion did not affect outcomes. Isolated CNS disease trended toward improved OS compared with combined CNS and BM (P = .12). R/R EM disease can be effectively treated with tisagenlecleucel; toxicity, relapse, and survival rates are comparable to those of patients with BM-only disease. Outcomes for isolated CNS relapse are encouraging.