Frontline Inotuzumab Ozogamicin plus Low-Intensity Chemotherapy (mini-hyper-CVD) for Older Patients with ALL
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.
- Kantarjian HM, et al. Lancet Oncol. 2012;13(4):403-411.
- Jabbour E, et al. ASH 2015. Abstract 83.