title: Inotuzumab ozogamicin in the management of acute lymphoblastic leukaemia.
abstract: Whilst most adult patients with acute lymphoblastic leukaemia will go into remission with standard induction chemotherapy, many will relapse. Response rates to standard salvage chemotherapy regimens are low and the outlook on relapse is very poor and associated with significant morbidity and mortality hence the need for newer targeted approaches. Inotuzumab ozogamicin (previously known as CMC-544) is an antibody-drug conjugate and consists of a monoclonal anti-CD22 antibody bound to calicheamicin. The target, CD22, is widely expressed on acute lymphoblastic leukaemia cells making it a potential therapeutic target. The calicheamicin is delivered intracellularly and causes leukaemia cell apoptosis. Overall response rates of 57% were observed in a Phase II study and the final results of a Phase III randomised controlled trial comparing this drug to the investigator choice 'standard of care' chemotherapy are eagerly awaited. Whilst initial results are promising, there have been concerns regarding liver toxicity and the incidence of veno-occlusive disease of the liver especially in patients who have previously received or go on to allogeneic stem cell transplant.
authors.affiliation: a Department of Haematology , Sheffield Teaching Hospitals , Sheffield , UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Morley
authors.affiliation: b Adult BMT Unit, Bristol Haematology and Oncology Centre , University Hospitals Bristol NHS Trust , Bristol , UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000080045:Inotuzumab Ozogamicin
keywords: Acute lymphoblastic leukaemia; CD22; Inotuzumab Ozogamicin; calicheamicin; relapse; veno-occlusive disease of the liver