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

Erica Brivio, André Baruchel, Auke Beishuizen, Jean Pierre Bourquin, Patrick A. Brown, Todd Cooper, Lia Gore, E. Anders Kolb, Franco Locatelli, Shannon L. Maude, Francis J. Mussai, Britta Vormoor-Bürger, Josef Vormoor, Arend von Stackelberg, C. Michel Zwaan*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

24 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalEuropean Journal of Cancer
Early online date1 Feb 2022
Publication statusPublished - 1 Mar 2022

Bibliographical note

Funding Information:
Most of the agents presented in the article were discussed during two editions of the New Agents in Leukaemia/Lymphoma meeting, 16?17 October 2018 and 27?28 October 2020, Utrecht, The Netherlands. The authors would like to thank the ITCC consortium and the COG group for the close collaboration during these meetings and for upcoming early clinical trials in paediatric oncology. They would also like to thank Leonie Kastaneer for all the logistic support necessary to organise the New Agents in Leukaemia/Lymphoma meetings and Astrid Danen-van Oorschot for collecting the information discussed during the meetings and helping in the writing phase.

Publisher Copyright:
© 2022 The Author(s)


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