Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia

Valeria Ceolin, Erica Brivio, Harm van Tinteren, Susan R. Rheingold, Allison Leahy, Britta Vormoor, Maureen M. O’Brien, Jeremy D. Rubinstein, Krzysztof Kalwak, Barbara De Moerloose, Elad Jacoby, Peter Bader, Mónica López-Duarte, Bianca F. Goemans, Franco Locatelli, Peter Hoogerbrugge, Friso G. Calkoen, Christian Michel Zwaan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chimeric antigen receptor T cells targeting CD19 (CART-19) have shown remarkable efficacy for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We investigated whether prior use of inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, may impact CAR T-cell manufacturing or efficacy via pre-CART-19 depletion of the B-cell compartment. In this international, retrospective analysis, 39 children and young adults receiving InO before (n = 12) and/or after (n = 27) T-cell apheresis as bridging therapy to CART-19 treatment were analyzed. Median age at infusion was 13 years (range 1.4–23 years). Thirty-four out of 39 patients (87.2%) obtained complete remission. With a median follow-up of 18.2 months after CART-19 infusion, 12-month event-free survival (EFS) was 53.3% (95% confidence interval (CI): 38.7–73.4) and overall survival (OS) was 77.8% (95% CI: 64.5–93.9). Seventeen patients (44%) relapsed with a median of 159 days (range 28–655) after CART-19 infusion. No difference in day 28 minimal residual disease negative complete response rate, 12-month OS/EFS, or incidence of CD19-positive or -negative relapses was observed among patients receiving InO before or after apheresis. Compared to published data for patients treated with CART-19 therapy without prior InO exposure, response and OS/EFS for patients treated with InO prior to CART-19 are similar.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalLeukemia
Volume37
Issue number1
DOIs
Publication statusE-pub ahead of print - 30 Oct 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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