Immunotherapy in B-Cell Acute Lymphoblastic Leukemia

In recent years, immunotherapy has been increasingly incorporated into the clinical care of both pediatric and adult patients with B-cell acute lymphoblastic leukemia (B-ALL) to improve outcomes. Four main categories of immunotherapies are used in B-ALL: (1) unconjugated monoclonal antibodies (mAbs), (2) antibody-drug conjugates (ADCs), (3) T-cell-engaging antibodies, and (4) CAR T cells. Although mAbs such as rituximab are primarily used in adults, the other modalities have demonstrated efficacy in both pediatric and adult patients with B-ALL. Among ADCs, inotuzumab ozogamicin (InO) has proven effective as monotherapy for relapsed disease, leading to FDA approval for patients aged >1 year with relapsed/refractory B-ALL. InO is also being investigated in the upfront setting in combination with chemotherapy. Although results in adults have been promising, increased rates of infectious complications in chemotherapy courses post-InO have hampered progress of trials in children, adolescents, and young adults. T-cell-engaging antibodies are now a standard component of therapy for most patients with newly diagnosed and relapsed B-ALL, following the successful integration of the bispecific T-cell-engager blinatumomab into chemotherapy regimens for both adults and children. Recent studies support the possibility of using blinatumomab to replace some or even most of the intensive chemotherapy traditionally used in B-ALL treatment. CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B-ALL by targeting CD19, but challenges remain due to the loss of CAR T-cell persistence and antigen escape. Newer CAR T cells targeting CD22 or the combination of CD19 and CD22 are being studied to address the issue of antigen escape. Overall, immune-based therapies are now a mainstay of B-ALL therapy. This article reviews the efficacy and safety data of several immune-based therapies in B-ALL and discusses a number of outstanding questions and possible future directions for the use of immune-based approaches in the treatment of B-ALL.