title: Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia.
abstract: 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.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. hkantarj@mdanderson.org
authors: Hagop
authors: H
authors: Kantarjian
authors: Deborah
authors: D
authors: Thomas
authors: Jeffrey
authors: J
authors: Jorgensen
authors: Partow
authors: P
authors: Kebriaei
authors: Elias
authors: E
authors: Jabbour
authors: Michael
authors: M
authors: Rytting
authors: Sergernne
authors: S
authors: York
authors: Farhad
authors: F
authors: Ravandi
authors: Rebecca
authors: R
authors: Garris
authors: Monica
authors: M
authors: Kwari
authors: Stefan
authors: S
authors: Faderl
authors: Jorge
authors: J
authors: Cortes
authors: Richard
authors: R
authors: Champlin
authors: Susan
authors: S
authors: O'Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000080045:Inotuzumab Ozogamicin; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D012008:Recurrence; D016879:Salvage Therapy; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis / Q000276:immunology; D033581:Stem Cell Transplantation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C497867:CD22 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; D000080045:Inotuzumab Ozogamicin
keywords: acute lymphocytic leukemia; inotuzumab; monoclonal antibody; refractory; relapsed
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