Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma.

Autor: Brivio E; Princess Ma´xima Center for Pediatric Oncology, Utrecht, the Netherlands; Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands., Baruchel A; Hématologie-Immunologie Pédiatrique, Hoˆ pital Universitaire Robert Debré (APHP) and Université de Paris, Paris, France., Beishuizen A; Princess Ma´xima Center for Pediatric Oncology, Utrecht, the Netherlands; Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands., Bourquin JP; Department of Oncology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Brown PA; Departments of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cooper T; Aflac Cancer and Blood Disorders Center/Children's Healthcare of Atlanta/Emory University, Atlanta, GA, USA., Gore L; University of Colorado School of Medicine and Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, USA., Kolb EA; Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I DuPont Hospital for Children, Wilmington, DE, USA., Locatelli F; Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome, Italy., Maude SL; Division of Oncology, Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Mussai FJ; Institute for Immunology and Immunotherapy, Cancer Research UK Birmingham Centre, The University of Birmingham, Birmingham, United Kingdom., Vormoor-Bürger B; Princess Ma´xima Center for Pediatric Oncology, Utrecht, the Netherlands., Vormoor J; Princess Ma´xima Center for Pediatric Oncology, Utrecht, the Netherlands; University Medical Center, Utrecht, the Netherlands; Newcastle University, Newcastle, UK., von Stackelberg A; Charité-Children's Hospital Berlin, Berlin, UK., Zwaan CM; Princess Ma´xima Center for Pediatric Oncology, Utrecht, the Netherlands; Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; The Innovative Therapies for Children with Cancer Consortium, Paris, France. Electronic address: c.m.zwaan@prinsesmaximacentrum.nl.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2022 Mar; Vol. 164, pp. 1-17. Date of Electronic Publication: 2022 Feb 01.
DOI: 10.1016/j.ejca.2021.12.029
Abstrakt: Despite improved outcomes achieved in the last decades for children with newly diagnosed leukaemia and lymphoma, treatment of patients with refractory/relapsed disease remains a challenge. The cure rate is still unsatisfactory and often achieved at the cost of significant morbidity. Exploring treatment with novel agents should offer less toxic therapeutic options, without compromising efficacy. Bispecific and antibody-drug conjugates targeting CD19 and CD22 (blinatumomab and inotuzumab ozogamicin) play an important role in the treatment of relapsed and refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL); antibodies targeting CD123 and CD38 are also under investigation for acute myeloid leukaemia (AML) and T-ALL, respectively. Targeted therapy with small molecules is of primary importance for specific genetic subtypes, such as BCR-ABL-positive ALL, FLT3-ITD AML and anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. KMT2A-directed targeted therapy with menin inhibitors holds promise to be of relevance in KMT2A-rearranged leukaemias, known to have dismal prognosis. Target inhibition in cellular pathways such as BCL-2, RAS, MEK, Bruton's tyrosine kinase, JAK-STAT or CDK4/CDK6 inhibition may be suitable for different diseases with common mutated pathways. Nevertheless, development and approval of new agents for paediatric cancers lags behind adult therapeutic options. New regulations were implemented to accelerate drug development for children. Considering the number of oncology medicinal products available for adults and the rarity of paediatric cancers, prioritisation based on scientific evidence and medical need, as well as international collaboration, is critical. Herein, we review the current status of drug development for children with leukaemia and lymphoma, excluding cellular therapy despite its well-known significance.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered potential competing interests: CMZ reports institutional funding was obtained from Pfizer, Jazz and Takeda to perform investigator-initiated studies with intent to file. Consultancy for Novartis, Takeda, Incyte, Roche Genentech. LG: advisory boards (unpaid) for Amgen, Genentech/Roche, Janssen, Kura and Pfizer; Stock/Stock options in Amgen, Mirati, OnKure and Sanofi Paris. SLM consulting, participation on advisory boards and study steering committees, clinical trial support: Novartis; Advisory board — Wugen. All other authors declare no conflict of interest.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: