The use of multiagent
combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with
acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several
surface antigens, including CD20, CD22, and CD19, which represent valuable targets for
immunotherapy.
Monoclonal antibodies,
antibody-drug conjugates, and bispecific T-cell-engaging
antibodies targeting these
antigens offer novel mechanisms of action. Within the last several years, the anti-CD20 antibody
rituximab has been added to
chemotherapy for newly diagnosed patients <60 years with CD20+
pre-B ALL and significantly improved the 2-year event-free survival from 52% to 65%. In adults with relapsed or refractory CD22+ ALL, the
antibody-drug conjugate inotuzumab ozogamicin resulted in a complete response rate of 81% and median overall survival of 7.7 months with reduced toxicity compared with standard
chemotherapy. Similarly, the bispecific T-cell-engaging antibody
blinatumomab yielded a complete response rate of 44% and a median overall survival of 7.7 months in an extensively treated ALL population. Moreover, ∼80% of ALL patients
in complete remission with evidence of
minimal residual disease (MRD) achieved a complete MRD response following treatment with
blinatumomab. These results highlight the tremendous promise of antibody-based treatment approaches for ALL. Ongoing and future research is critical to further define the role of the various
immunotherapies in the frontline treatment of ALL. Additional challenges include the optimal sequencing of the available
antibodies in the relapsed setting as well as their integration with stem cell transplant and
chimeric antigen receptor T-cell
therapy.