Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
04 2019
Historique:
received: 03 06 2018
accepted: 16 08 2018
revised: 09 08 2018
pubmed: 30 9 2018
medline: 10 8 2019
entrez: 30 9 2018
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30267011
doi: 10.1038/s41375-018-0265-z
pii: 10.1038/s41375-018-0265-z
pmc: PMC6438769
mid: NIHMS1504105
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Antineoplastic Agents 0
Inotuzumab Ozogamicin P93RUU11P7

Types de publication

Journal Article

Langues

eng

Pagination

884-892

Subventions

Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : NULL
ID : Z99 CA999999
Pays : International

Commentaires et corrections

Type : ErratumIn

Références

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Auteurs

Deepa Bhojwani (D)

Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. dbhojwani@chla.usc.edu.

Richard Sposto (R)

Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Nirali N Shah (NN)

National Cancer Institute, Bethesda, MD, USA.

Vilmarie Rodriguez (V)

Mayo Clinic, Rochester, MN, USA.

Constance Yuan (C)

National Cancer Institute, Bethesda, MD, USA.

Maryalice Stetler-Stevenson (M)

National Cancer Institute, Bethesda, MD, USA.

Maureen M O'Brien (MM)

Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA.

Jennifer L McNeer (JL)

University of Chicago Medicine Comer Children's Hospital, Chicago, IL, USA.

Amrana Quereshi (A)

Oxford University Hospitals, Oxford, UK.

Aurelie Cabannes (A)

University Hospital Saint-Louis, Paris, France.

Paul Schlegel (P)

University Children's Hospital of Würzburg, Würzburg, Germany.

Claudia Rossig (C)

University Children's Hospital of Münster, Münster, Germany.

Luciano Dalla-Pozza (L)

Children's Hospital at West-mead, Sydney, Australia.

Keith August (K)

Children's Mercy Hospital, Kansas City, MO, USA.

Sarah Alexander (S)

The Hospital for Sick Children, Toronto, Canada.

Jean-Pierre Bourquin (JP)

University Children's Hospital, Zurich, Switzerland.

Michel Zwaan (M)

Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Elizabeth A Raetz (EA)

New York University Langone Medical Center, New York, NY, USA.

Mignon L Loh (ML)

Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

Susan R Rheingold (SR)

Childrens Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

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