Cutting to the Front of the Line: Immunotherapy for Childhood Acute Lymphoblastic Leukemia
Jennifer L. McNeer, Rachel E. Rau, Sumit Gupta, Shannon L. Maude, Maureen M. O’Brien
Abstract
Although many children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) are cured with modern, risk-adapted chemotherapy regimens, 10% to 15% of patients will experience relapse or have refractory disease. Recent efforts to further intensify cytotoxic chemotherapy regimens in the frontline setting have failed as a result of excessive toxicity or lack of improvement in efficacy. As a result, novel approaches will be required to achieve cures in more newly diagnosed patients. Multiple immune-based therapies have demonstrated considerable efficacy in the setting of relapsed or refractory (R/R) disease, including CD19 targeting with blinatumomab and tisagenlecleucel and CD22 targeting with inotuzumab ozogamicin. These agents are now under investigation by the Children's Oncology Group (COG) in clinical trials for newly diagnosed B-ALL, with integration into standard chemotherapy regimens based on clinically and biology-based risk stratification as well as disease response.