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
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Department of Pediatric Oncology/Hematology, Regina Margherita Children's Hospital, University of Turin, Turin, Italy.
Leukemia. 2023 Jan;37(1):53-60. doi: 10.1038/s41375-022-01740-9. Epub 2022 Oct 30.
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.
靶向CD19的嵌合抗原受体T细胞（CART-19）已显示出对复发/难治性（R/R）B细胞前体急性淋巴细胞白血病（BCP-ALL）具有显著疗效。我们研究了预先使用因诺妥珠单抗奥佐米星（InO）（一种与卡奇霉素偶联的抗CD22抗体）是否会通过在CART-19治疗前使B细胞区室耗竭而影响CAR T细胞的制备或疗效。在这项国际回顾性分析中，对39名儿童和青年成人进行了分析，这些患者在进行T细胞采集作为CART-19治疗的桥接治疗之前（n = 12）和/或之后（n = 27）接受了InO治疗。输注时的中位年龄为13岁（范围1.4 - 23岁）。39名患者中有34名（87.2%）获得完全缓解。在CART-19输注后中位随访18.2个月时，12个月无事件生存率（EFS）为53.3%（95%置信区间（CI）：38.7 - 73.4），总生存率（OS）为77.8%（95% CI：64.5 - 93.9）。17名患者（44%）在CART-19输注后复发，中位复发时间为159天（范围28 - 655天）。在采集前或采集后接受InO治疗的患者中，未观察到第28天微小残留病阴性完全缓解率、12个月OS/EFS或CD19阳性或阴性复发发生率的差异。与未预先接触InO而接受CART-19治疗的患者的已发表数据相比，在CART-19之前接受InO治疗的患者的缓解情况和OS/EFS相似。
