New monoclonal antibodies for the treatment of acute lymphoblastic leukemia

While the majority of pediatric acute lymphoblastic leukemia (ALL) patients can be cured with combination chemotherapy, novel immunotherapies have provided new treatment options for those with relapsed or refractory disease. In adults, ALL remains challenging to treat, with incremental advances delivered by optimization of cytotoxic chemotherapy regimens and supportive care, integration of tyrosine kinase inhibitor therapies for BCR-ABL-positive disease, and the development of novel immunotherapies. Rituximab, in combination with established chemotherapy regimens, reduces relapse in 30%-50% of patients who have CD20-positive disease. In the past decade, antibody-drug conjugates, bispecific antibodies (immune cell engagers), and CAR-T cell therapies utilizing monoclonal antibody (mAb) technology have entered clinical practice, initially presenting important treatment options for patients with relapsed or refractory disease. Beyond this, a variety of antibody-derived therapies are being investigated, including for the treatment of T-cell ALL, a subtype of the disease for which it has been more challenging to identify a suitable tumor-associated antigen. These new generations of ALL immunotherapies possess both common and distinct mechanisms of resistance that investigational therapies aim to overcome. In this chapter, we review the landscape of licensed and investigational mAb-derived therapies for ALL.