Feasibility of Allografting in Patients with Advanced Acute Lymphoblastic Leukemia After Salvage Therapy With Inotuzumab Ozogamicin

Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody that targets B lymphocytes in early stages of development, successfully inducing remission in patients with relapsed acute lymphoblastic leukemia (ALL). We report our experience of 26 patients who were treated with IO followed by allogeneic stem cell transplantation (SCT). Background: No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin that targets B lymphocytes in early stages of development, successfully inducing remission in patients with multiply relapsed ALL. Methods: We describe our findings in 26 patients who received allogeneic hematopoietic stem cell transplantation (SOT) after treatment with 10 between September 2010 and October 2011. Results: Patients with a median age of 33 years (range, 5-70 years) received an allogeneic matched sibling donor (n = 9), matched- or 1-antigen mismatched unrelated donor (n = 16), or cord blood donor SCT (n = 1) while in complete remission (n = 23) or with active disease (n = 3). At the time of SCT, 15 patients were in complete remission without evidence of minimal residual disease (MRD) measured by multiparameter flow cytometry. Patients were heavily pretreated, including 5 patients who had received previous allogeneic SCT. Patients received a median of 3 courses of IO (range, 1-5 courses) before SOT. Seven patients are alive at a median follow-up of 13 months (range, 5-16 months), with 1-year event-free and overall survival (OS) of 22% and 20%, respectively. Patients without MRD at time of SOT had a markedly better 1-year OS of 42%. The cumulative incidence of nonrelapse mortality (NRM) at 6 months and 1 year were 40% and 60%, respectively, with 5 deaths attributed to venoocclusive disease (VOD). Conclusions: Treatment with IO allows more patients to undergo transplantation while in remission, with favorable overall survival in patients without MRD who undergo transplantation. Reduction in hepatic toxicity is needed to improve overall results. (c) 2013 Elsevier Inc. All rights reserved.