Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia

Cancer. 2013 Aug 1;119(15):2728-36. doi: 10.1002/cncr.28136. Epub 2013 Apr 30.


Background: CD22 expression occurs in >90% of patients with acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, is active in ALL.

Methods: Patients with refractory-relapsed ALL received treatment with inotuzumab. The first 49 patients received single-dose, intravenous inotuzumab at doses of 1.3 to 1.8 mg/m2 every 3 to 4 weeks. In the next 41 patients, the schedule was modified to inotuzumab weekly at a dose of 0.8 mg/m2 on day 1 and at a dose of 0.5 mg/m2 on days 8 and 15, every 3 to 4 weeks, based on higher in vitro efficacy with more frequent exposure.

Results: Ninety patients were treated; 68% were in salvage 2 or beyond. Overall, 17 patients (19%) achieved a complete response (CR), 27 (30%) had a CR with no platelet recovery (CRp), and 8 (9%) had a bone marrow CR (no recovery of counts), for an overall response rate of 58%. Response rates were similar for single-dose and weekly dose inotuzumab (57% vs 59%, respectively). The median survival was 6.2 months overall, 5.0 months with the single-dose schedule, and 7.3 months with the weekly dose schedule. The median survival was 9.2 months for patients in salvage 1 (37% at 1 year), 4.3 months for patients in salvage 2, and 6.6 months for patients in salvage 3 or later. The median remission duration was 7 months. Reversible bilirubin elevation, fever, and hypotension were observed less frequently on the weekly dose. In total, 36 of 90 patients (40%) underwent allogeneic stem cell transplantation. Veno-occlusive disease was noted in 6 of 36 patients after stem cell transplantation (17%), was less frequent after the weekly schedule (7%), and with less alkylators in the preparative regimen.

Conclusions: Inotuzumab single-agent therapy was highly active, safe, and convenient in patients with refractory-relapsed ALL. A weekly dose schedule appeared to be equally effective and less toxic than a single-dose schedule.

Keywords: acute lymphocytic leukemia; inotuzumab; monoclonal antibody; refractory; relapsed.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Inotuzumab Ozogamicin
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery
  • Recurrence
  • Salvage Therapy
  • Sialic Acid Binding Ig-like Lectin 2 / biosynthesis
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • Stem Cell Transplantation
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • CD22 protein, human
  • Sialic Acid Binding Ig-like Lectin 2
  • Inotuzumab Ozogamicin