An Update on Clinical Trials and Potential Therapeutic Strategies in T-Cell Acute Lymphoblastic Leukemia

Current therapies for T-cell acute leukemia are based on risk stratification and have greatly improved the survival rate for patients, but mortality rates remain high owing to relapsed disease, therapy resistance, or treatment-related toxicities/infection. Patients with relapsed disease continue to have poor outcomes. In the past few years, newer agents have been investigated to optimize upfront therapies for higher-risk patients in the hopes of decreasing relapse rates. This review summarizes the progress of chemo/targeted therapies using Nelarabine/Bortezomib/CDK4/6 inhibitors for T-ALL in clinical trials and novel strategies to target NOTCH-induced T-ALL. We also outline immunotherapy clinical trials using monoclonal/bispecific T-cell engaging antibodies, anti-PD1/anti-PDL1 checkpoint inhibitors, and CAR-T for T-ALL therapy. Overall, pre-clinical studies and clinical trials showed that applying monoclonal antibodies or CAR-T for relapsed/refractory T-ALL therapy is promising. The combination of target therapy and immunotherapy may be a novel strategy for T-ALL treatment.

Automated summary

Current therapies for T-cell acute leukemia have improved survival rates, but high mortality rates remain due to relapsed disease, resistance, and toxicities/infection. Newer agents are being investigated to optimize upfront therapies and decrease relapse rates. This review summarizes the progress of chemo/targeted therapies and novel strategies for T-cell acute leukemia, as well as immunotherapy clinical trials using antibodies and CAR-T therapy. The combination of targeted therapy and immunotherapy may be a promising approach.