Current Management of Adult Acute Lymphoblastic Leukaemia: Emerging Insights and Outstanding Questions

Abstract

Less than 50% of patients with adult acute lymphoblastic leukaemia (ALL) experience long-term survival and for those adults >60 years old, long-term survival rates are only 10%. However, significant advances have been reported over the last decade. Both the efficacy of chemotherapy and the safety of transplants have improved. Improved outcomes have been seen in younger adults treated with paediatric-inspired chemotherapy regimens. Minimal residual disease has been identified as an independent predictor of relapse risk and is currently widely used for risk-adapted treatment. Newly developed targeted therapies have been developed to improve treatment outcomes. Tyrosine kinase inhibitors (TKI) have become an integral part of front-line therapy for Philadelphia (Ph) chromosome positive ALL. Ph-positive ALL serves as the first example of truly targeted treatment, although the choice of the most effective TKI is not yet settled. The last few years have also seen a surge in immune therapies for B cell lineage ALL. The success of the anti-CD20 monoclonal antibody rituximab provided proof-of-principle for exploiting the immune system therapeutically. Novel immune therapies recruit (bispecific T cell engager) or modify (chimeric antigen receptor T cells) the patient’s own T cells to fight leukaemic cells. These new approaches led us to predict that ALL therapy might be based heavily on non-chemotherapeutic approaches in the near future. The role of allogeneic stem cell transplantation is also increasingly called into question. Herein, we review the background and development of these distinct treatments, and assess the current clinical knowledge of their efficacy and safety.