Acute lymphoblastic leukemia (ALL) is a
hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic
chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Current
immunotherapies exploit the performance of
antibodies through several different mechanisms, including naked
antibodies,
antibodies linked to
cytotoxic agents, and T-cell re-directing
antibodies. Compared with
chemotherapy, the application of an
antibody-drug conjugates (ADC) called
inotuzumab ozogamicin in relapsed or refractory (R/R) CD22+. ALL resulted in a complete remission (CR) rate of 81% and an overall median survival of 7.7 months with reduced toxicity. Similarly,
blinatumomab, the first FDA-approved bispecific antibody (BsAb), produced a 44% complete response rate and an overall median survival of 7.7 months in a widely treated ALL population. In addition, approximately 80% of patients getting complete remission with evidence of
minimal residual disease (MRD) achieved a complete MRD response with the use of
blinatumomab. These results highlight the great promise of antibody-based
therapy for ALL. How to reasonably determine the place of antibody drugs in the treatment of ALL remains a major problem to be solved for ongoing and future researches. Meanwhile the combination of antibody-based
therapy with traditional standard of care (SOC)
chemotherapy,
chimeric antigen receptor (CAR) T-cell therapy and HSCT is also a challenge. Here, we will review some important milestones of antibody-based
therapies, including combinational strategies, and
antibodies under clinical development for ALL.