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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenpeer review

24 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)1-17
Aantal pagina's17
TijdschriftEuropean Journal of Cancer
StatusGepubliceerd - mrt. 2022


Duik in de onderzoeksthema's van 'Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma'. Samen vormen ze een unieke vingerafdruk.

Citeer dit