Inotuzumab Ozogamicin as First-Line Therapy in Acute Lymphoblastic Leukemia

The long-term outcome of older patients with acute lymphoblastic leukemia (ALL) is poor due to a reduced ability to tolerate intensive chemotherapy, a more aggressive disease biology, and the presence of comorbidities. Older adults with Philadelphia chromosome-negative (Ph-) B-cell ALL have the highest rates of treatment failure and complications, and the pediatric-inspired regimens that are effective in younger adults are severely limited by their toxicity in older patients. Targeted therapies, including inotuzumab ozogamicin (InO) and blinatumomab, have potent activity in B-cell ALL and are used today as single agents, and in combination with chemotherapy in both salvage and frontline ALL therapy. Optimized frontline use of B-cell targeting agents would potentially reduce the need for, and exposure to, conventional chemotherapy and improve the tolerance and efficacy of reduced-intensity chemotherapy regimens combined with targeted therapies. This review summarizes the efficacy and safety results of several recent trials investigating different approaches with InO as first-line therapy in patients with Ph- B-cell ALL.