Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1-18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m2. Using a single-stage design, with an overall response rate (ORR) ≤ 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9-93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49-20.07). One year Event Free Survival was 36.7% (95% CI: 22.2-60.4%), and Overall Survival was 55.1% (95% CI: 39.1-77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.

Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands

Department of Hematology Oncology and of Cell and Gene Therapy IRCCS Ospedale Pediatrico Bambino Gesú Sapienza University of Rome Rome Italy

Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands

Department of pediatric Hematology and Oncology Hopital Armand Trousseau APHP Sorbonne Université Paris France

Department of Pediatric Hematology and Oncology University Hospital Motol Prague Czech Republic

Department of Pediatric Oncology and Hematology Hospital Niño Jesús Madrid Spain

Department of Pediatric Oncology Erasmus MC Sophia Children's Hospital Rotterdam the Netherlands

Department of Pediatric Oncology Essen University Hospital Essen Germany

Department of Pediatrics Division of Oncology and Hematology Charité Universitätsmedizin Berlin Berlin Germany

Department of Pediatrics Rostock University Medical Centre Rostock Germany

Division of Pediatric Hematology and Oncology Sheba Medical Center Ramat Gan Israel

Institut de Recerca Sant Joan de Déu Barcelona Spain

Institute of Pediatric Hematology and Oncology Civil Hospital of Lyon Claude Bernard University Lyon France

IntReALL study group Berlin Germany

Oncode Institute Utrecht the Netherlands

Pediatric Hematology and Oncology University Children's Hospital Muenster Münster Germany

Pediatric Hematology Hôpital Jeanne de Flandre CHRU de Lille Lille France

Pediatric Hematology Oncology Unit Department of Pediatrics MBBM Foundation ASST Monza University of Milano Bicocca Monza Italy

Pediatric Oncology and Hematology Department Hospital Sant Joan de Déu de Barcelona Barcelona Spain

Pfizer Inc Groton CT USA

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

Service d'Hématologie Immunologie Oncologie Hôpital des Enfants CHU Toulouse Toulouse France

Service Onco Hématologie Pédiatrique Hôpital Mère Enfant Nantes University Hospital Nantes France

St Anna Children's Hospital Medical University of Vienna Vienna Austria

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