CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study

Elad Jacoby, Sara Ghorashian, Britta Vormoor, Barbara De Moerloose, Nicole Bodmer, Olga Molostova, Asaf D. Yanir, Jochen Buechner, Ronit Elhasid, Bella Bielorai, Srdan Rogosic, Marie Emilie Dourthe, Michael Maschan, Claudia Rossig, Amos Toren, Arend von Stackelberg, Franco Locatelli, Peter Bader, Martin Zimmermann, Jean Pierre BourquinAndre Baruchel

Research output: Contribution to journalArticlepeer-review

Abstract

Relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may occur in the central nervous system (CNS). Most clinical trials of CAR T-cell therapy excluded patients with active CNS leukemia, partially for concerns of neurotoxicity. Here, we report an international study of fifty-five children and adolescents who received CAR T-cell therapy for relapsed BCP-ALL with CNS involvement at the time of referral. All patients received bridging therapy, 16 still having active CNS disease at the time of lymphodepletion. Twelve patients received CD28-based CAR T-cells, 9 being subsequently treated with allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Forty-three patients received 4-1BB-based CAR T-cells. Cytokine-release syndrome (CRS) and neurotoxicity occurred in 65% and 38% of patients, respectively, more frequently following treatment with CD28-based CARs. Fifty-one of 54 evaluable patients (94%) achieved complete response following this therapy. Relapse occurred in 22 patients: 19/43 following 4-1BB-based CARs (12 CNS relapses), and 3/12 after CD28-based CARs with subsequent HSCT (no CNS relapse). Patients treated with tisagenlecleucel for an isolated CNS relapse had a high incidence of a subsequent CNS relapse (6 of 8). CAR T-cells were found to be effective in this cohort, though the risk of CNS relapse was not completely mitigated by this approach.

Original languageEnglish
Pages (from-to)1525-1532
Number of pages8
JournalLeukemia
Volume36
Issue number6
DOIs
StatePublished - Jun 2022

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