title: Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study.
abstract: BACKGROUND
  The outlook for patients with refractory and relapsed acute lymphocytic leukaemia (ALL) is poor. CD22 is highly expressed in patients with ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin calecheamicin. We did a phase 2 study to assess the efficacy of this antibody.
  
  
  METHODS
  We recruited patients at the MD Anderson Cancer Center, Houston, TX, USA, between June, 2010, and March, 2011. Adults and children with refractory and relapsed ALL were eligible. Ten adults were treated before enrolment of children started. Patients were given 1·8 mg/m(2) inotuzumab ozogamicin intravenously over 1 h every 3-4 weeks (the first three adults and three children received 1·3 mg/m(2) in the first course). The primary endpoint was overall response (complete response or marrow complete response with no recovery of platelet count or incomplete recovery of neutrophil and platelet counts). Analysis was done by intention to treat. This study is registered, number NCT01134575.
  
  
  RESULTS
  49 patients were enrolled and treated. Median age was 36 years (range 6-80). CD22 was expressed in more than 50% of blasts in all patients. The median number of courses was two (range one to five) and the median time between courses was 3 weeks (range 3-6). Nine (18%) patients had complete response, 19 (39%) had marrow complete response, 19 (39%) had resistant disease, and two (4%) died within 4 weeks of starting treatment. The overall response rate was 57% (95% CI 42-71). The most frequent adverse events during course one of treatment were fever (grade 1-2 in 20 patients, grade 3-4 in nine), hypotension (grade 1-2 in 12 patients, grade 3 in one), and liver-related toxic effects (bilirubin: grade 1-2 in 12 patients, grade 3 in two; raised aminotransferase concentration: grade 1-2 in 27 patients, grade 3 in one).
  
  
  CONCLUSIONS
  Inotuzumab ozogamicin shows promise as a treatment for refractory and relapsed ALL.
  
  
  BACKGROUND
  Pfizer.
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jorgensen
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Michael
authors.initials: M
authors.lastname: Rytting
authors.forename: Sergernne
authors.initials: S
authors.lastname: York
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Monica
authors.initials: M
authors.lastname: Kwari
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Robert
authors.initials: R
authors.lastname: Tarnai
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Anjali
authors.initials: A
authors.lastname: Advani
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D053281:Enediynes / Q000008:administration & dosage; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D008875:Middle Aged; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D016019:Survival Analysis; D014481:United States
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C497867:CD22 protein, human; D053281:Enediynes; D051918:Sialic Acid Binding Ig-like Lectin 2; D000080045:Inotuzumab Ozogamicin