Document Type

Article

Publication Date

4-2019

Identifier

DOI: 10.1038/s41375-018-0265-z; PMCID: PMC6438769

Abstract

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.

Journal Title

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

Volume

33

Issue

4

First Page

884

Last Page

892

MeSH Keywords

Adolescent; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance, Neoplasm; Female; Humans; Inotuzumab Ozogamicin; Male; Neoplasm Recurrence, Local; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Young Adult

Keywords

Adolescent; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance, Neoplasm; Female; Humans; Inotuzumab Ozogamicin; Male; Neoplasm Recurrence, Local; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Young Adult

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Publisher's Link: https://www.nature.com/articles/s41375-018-0265-z

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