TY - JOUR
T1 - Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia
AU - Ceolin, Valeria
AU - Brivio, Erica
AU - Van Tinteren, Harm
AU - Rheingold, Susan R.
AU - Leahy, Allison
AU - Vormoor, Britta
AU - O’Brien, Maureen M.
AU - Rubinstein, Jeremy D.
AU - Kalwak, Krzysztof
AU - De Moerloose, Barbara
AU - Jacoby, Elad
AU - Bader, Peter
AU - López-Duarte, Mónica
AU - Goemans, Bianca F.
AU - Locatelli, Franco
AU - Hoogerbrugge, Peter
AU - Calkoen, Friso G.
AU - Zwaan, Christian Michel
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - CAR-T
KW - CAR-T
UR - http://hdl.handle.net/10807/229888
U2 - 10.1038/s41375-022-01740-9
DO - 10.1038/s41375-022-01740-9
M3 - Article
SN - 0887-6924
VL - 37
SP - 53
EP - 60
JO - Leukemia
JF - Leukemia
ER -