Current Advances in Treatment Strategies for Relapsed T-ALL in Children

Abstract

In children, acute lymphoblastic leukaemia (ALL) is the most common form of cancer. For B-ALL the 5-year survival rates are improving reaching 90%. However, T-ALL lags behind with survival rates of 80-85% as 20% of the patients experience relapse. Relapsed patients have a low survival rate of only 25%. Therefore, new treatments for relapsed T-ALL in children are urgently needed. Rather than using chemotherapy, which can be quite toxic, there is now a growing research focus on targeted therapies. This review evaluates the results of clinical trials involving targeted therapies for T-ALL to identify the most promising treatments. Targeted therapies discussed include inhibition of BCL-2, the proteasome, CDK4/CDK6, ABL/SRC kinases, and the NOTCH1, IL-7R/JAK/STAT, PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways. Additionally, immunotherapies such as monoclonal and bispecific antibodies and CAR-T therapy are discussed. The highest CR responses have been observed with BCL-2 inhibition using venetoclax, proteasome inhibition using bortezomib and CD38 targeting with the monoclonal antibody daratumumab. However, due to the heterogeneous nature of T-ALL, no single treatment is universally effective. The key to improving survival chances for relapsed paediatric T-ALL patients lies in selecting a combination of these targeted therapies based on the genetic profile of the patient’s tumour.