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

• Published in: Leukemia Vol. 37; no. 1; pp. 53 - 60
• Main Authors: Ceolin, Valeria, Brivio, Erica, van Tinteren, Harm, Rheingold, Susan R., Leahy, Allison, Vormoor, Britta, O’Brien, Maureen M., Rubinstein, Jeremy D., Kalwak, Krzysztof, De Moerloose, Barbara, Jacoby, Elad, Bader, Peter, López-Duarte, Mónica, Goemans, Bianca F., Locatelli, Franco, Hoogerbrugge, Peter, Calkoen, Friso G., Zwaan, Christian Michel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2023; Nature Publishing Group
• Subjects: 631/532; 631/67; 82/1; Acute lymphoblastic leukemia; Adolescent; Adult; Antibodies; Antigens; Apheresis; Calicheamicin; Cancer Research; CD19 antigen; CD22 antigen; Cell therapy; Cell- and Tissue-Based Therapy; Child; Child, Preschool; Children; Chimeric antigen receptors; Critical Care Medicine; Depletion; Effectiveness; Hematology; Humans; Infant; Inotuzumab Ozogamicin; Intensive; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine; Medicine & Public Health; Minimal residual disease; Monoclonal antibodies; Oncology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Receptors; Receptors, Chimeric Antigen; Remission; Retrospective Studies; Survival; Targeted cancer therapy; Therapy; Young Adult; Young adults
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-022-01740-9

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.