Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial

Edoardo Pennesi, Naomi Michels, Erica Brivio, Vincent H J van der Velden, Yilin Jiang, Adriana Thano, Anneke J C Ammerlaan, Judith M Boer, H Berna Beverloo, Barbara Sleight, Ying Chen, Britta Vormoor-Bürger, Susana Rives, Bella Bielorai, Claudia Rössig, Arnaud Petit, Carmelo Rizzari, Gernot Engstler, Jan Starý, Francisco J Bautista SirventChristiane Chen-Santel, Benedicte Bruno, Yves Bertrand, Fanny Rialland, Geneviève Plat, Dirk Reinhardt, Luciana Vinti, Arend Von Stackelberg, Franco Locatelli, Christian M Zwaan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1516-1524
Number of pages9
JournalLeukemia
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 2022

Keywords

  • Acute Disease
  • Adolescent
  • Calicheamicins
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Inotuzumab Ozogamicin
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  • Progression-Free Survival

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