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. 2022 Dec 9;2022(1):611-617.
doi: 10.1182/hematology.2022000359.

Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy

Rishi S Kotecha  1   2   3
Affiliations

Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy

Rishi S Kotecha. Hematology Am Soc Hematol Educ Program. .

Abstract

Outcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival. We have now entered an era of immunotherapy with integration of agents, such as blinatumomab or chimeric antigen receptor T-cell therapy, into the standard chemotherapy backbone, showing significant promise for improving the dismal outcomes for this disease. There remains much optimism for the future as a wealth of preclinical studies have identified additional novel targeted agents, such as venetoclax or menin inhibitors, ready for incorporation into treatment, providing further ammunition to combat this aggressive disease. In contrast, infants with KMT2A-germline ALL have demonstrated excellent survival outcomes with current therapy, but there remains a high burden of treatment-related morbidity. Greater understanding of the underlying blast genetics for infants with KMT2A-germline ALL and incorporation of immunotherapeutic approaches may enable a reduction in the intensity of chemotherapy while maintaining the excellent outcomes.

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Conflict of interest statement

Rishi S. Kotecha has participated in Scientific Advisory Boards for Amgen, Link Healthcare, and Jazz Pharmaceuticals.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Immunotherapeutic approaches for the treatment of infants with acute lymphoblastic leukemia. mAb, monoclonal antibody.
Figure 2.
Figure 2.
Novel drug classes for the treatment of infants with KMT2A-rearranged acute lymphoblastic leukemia.
See this image and copyright information in PMC

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