Emerging therapeutic options in acute lymphoblastic leukemia

Immunotherapies have dramatically increased response rates in the relapsed/refractory setting of acute lymphoblastic leukemia. These emerging therapeutic options include blinatumomab, a bispecific T-cell engager construct; inotuzumab, an antibody–drug conjugate; and CAR T cells. Despite significantly improved rates of response, however, CAR T-cell therapy is the only approach associated with durable survival in a significant proportion of patients. Immunotherapies come with characteristic toxicity profiles. Inotuzumab is associated with hepatotoxicity, and blinatumomab and CAR T cells are associated with both cytokine release syndrome and neurotoxicity. Furthermore, immunotherapy is not always successful. Several mechanisms of failure exist, including failure to manufacture the CAR product, failure to engraft or lack of persistence of CAR T cells, endogenous T cell or CAR T-cell exhaustion, and antigen escape.