Elderly patients with acute lymphoblastic leukemia (ALL) show poor tolerance of intensive chemotherapy, which is the rationale for evaluation of targeted nonmyelosuppressive agents in combination with effective low-intensity chemotherapy in this population. Inotuzumab ozogamicin (IO) is an anti-CD22 monoclonal antibody conjugate that has shown single-agent activity in relapsed/refractory ALL.1 Jabbour and colleagues reported on results of a phase 1/2 study of frontline IO plus a low-intensity mini-hyper-CVD induction regimen in older patients (?60 years) with newly diagnosed ALL; mini-hyper-CVD consisted of cyclophosphamide/dexamethasone at 50% dose reduction, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2, omitting anthracycline.2 At a median follow-up of 19 months, 34 (97%) of 35 evaluable patients achieved a response, including 28 complete responses (CRs) and 6 CRs with incomplete platelet recovery. All patients who achieved CRs also achieved cytogenetic CR and flow-cytometry minimal residual disease–negative status. The 2-year CR duration was 81%, and 2-year overall survival was 64%. After induction, median time to platelet recovery was 23 days and that to neutrophil recovery was 16 days. Four (12%) patients received consolidation chemotherapy; 16 (47%) patients received maintenance chemotherapy. Grade 3/4 toxicities included prolonged thrombocytopenia (74%), infections during consolidation (74%), infections during induction (52%), hyperglycemia (50%), hypokalemia (35%), hyperbilirubinemia (21%), increased alanine transaminase/aspartate transaminase (24%), and hemorrhage (18%); 4 patients (11%) reported veno-occlusive disease. Eleven (32%) deaths were reported; 2 of which were due to disease progression, 2 due to veno-occlusive disease, and 3 patients died in CR from sepsis. Based on these results, IO plus low-intensity mini-hyper-CVD chemotherapy appears to be well-tolerated and efficacious in the frontline setting in older patients with ALL, representing a less-intense option for this patient population.