Emerging Monoclonal Antibody Therapy for the Treatment of Acute Lymphoblastic Leukemia

The treatment of adults with ALL has undergone tremendous progress over the past 15 years. The advances have been particularly marked with B-lineage ALL. The development of bispecific antibodies directed against CD19 ushered in a new era in overcoming persistent minimal disease in newly diagnosed ALL patients as well as successfully treating those with relapsed disease. The immune-conjugates targeting CD22 have also had a similarly impressive role in improving the outcome in such patients. These advances are now being extended to frontline regimens for B-lineage ALL, including the Philadelphia-chromosome-positive subtype. Over the past decade, the development of chimeric antigen receptor T-cell therapy (CAR-T) has ushered in a new era, opening up hope when none was available for patients with particularly advanced disease. Such advances come at a considerable price for toxicity, which, however, are lessening with experience and the development of new agents to ameliorate some of the toxicities. Unfortunately, the progress for T-cell in ALL has lagged behind that of B-lineage ALL. Of late, however, there are preliminary results of potentially exciting data using monoclonal antibodies against CD38, in the form of daratumumab, and it is hoped that these will lead to an equally successful advance in the treatment of T-ALL. Despite all these advances, ALL in adults remains a formidable disease. While ongoing progress is being made, also in the therapy of older patients, we are still lagging behind the almost totally curative potential of current therapy for childhood ALL.