T-cell acute lymphoblastic leukemia in adults: current treatment approaches and future perspectives

The therapeutic landscape of acute lymphoblastic leukemia (ALL) in adults has greatly changed thanks to the introduction of response-adapted pediatric-inspired regimens and, in B-ALL, the advent of immunotherapy. More recently, the better understanding of genetics, the encouraging results of new agents and the evidence of activity of monoclonal antibodies and CAR-T cells are opening the road for meaningful advances in T-ALL.

We discuss the current therapeutic scenario of T-ALL in adults, including the basis of relevant chemotherapy backbones and a summary of recent biological advances with potential clinical implications. Besides, we summarize data of new drugs explored in the relapsed/refractory (R/R) setting and how they are moving frontline, including a focus of the emerging role of immunotherapy.

The availability of effective agents like venetoclax, bortezomib and daratumumab may lead to improved frontline regimens, which will be tailored according to patient's genetics and drug response profile, and relevant role of CAR-T cell is foreseen, possibly beyond R/R setting. While several issues will require further studies, including central nervous system prophylaxis and treatment optimization in young adults and older patients, these advances will ultimately lead to improved efficacy, reduced toxicities and limited indications of allo-HCT.