{"entity":{"id":"gemtuzumab-ozogamicin","kind":"drug","name":"Gemtuzumab ozogamicin","aka":[],"tldr":"Gemtuzumab ozogamicin (Mylotarg) is an anti-CD33 antibody linked to the DNA-cutting payload calicheamicin, the first ADC approved, in 2000 for relapsed acute myeloid leukaemia. An unstable linker and no benefit in a confirmatory trial led to withdrawal in 2010; it returned in 2017 at a lower fractionated dose, with liver toxicity, including veno-occlusive disease, its defining risk.","summary":"Gemtuzumab ozogamicin (Mylotarg) is a humanised anti-CD33 IgG4 antibody linked through an acid-labile hydrazone to calicheamicin, a DNA cleaver that causes double-strand breaks, at a drug-to-antibody ratio of about 2 to 3. It was the very first ADC, approved in 2000 for relapsed CD33-positive AML, but this first-generation design had an unstable linker and heterogeneous conjugation, and it was withdrawn in 2010 after a confirmatory trial showed no benefit and excess deaths. Re-approval in 2017 was based on ALFA-0701, in which fractionated dosing (3 mg/m² on days 1, 4 and 7 with induction chemotherapy) improved event-free survival in CD33-positive AML. Hepatotoxicity including veno-occlusive disease, haemorrhage and infection are the key risks, so liver tests are checked before each dose. Its history shows that schedule and linker chemistry can decide the fate of a sound target.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Gemtuzumab_ozogamicin","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Gemtuzumab%20ozogamicin"}],"tags":[],"related":["cd33-expression"],"cancers":["aml","aml-paediatric"],"sections":[],"technologies":["adc"],"targets":["cd33"],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["hydrazone"],"trials":["aaml0531"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Mylotarg","modality":"ADC","payload":"Calicheamicin (DNA cleaver), DAR ~2-3","linker":"Acid-labile hydrazone","mechanism":"Anti-CD33 humanised IgG4 with calicheamicin; DNA double-strand cleavage.","approvals":[{"region":"US","year":2000,"indication":"Relapsed CD33+ AML (withdrawn 2010)"},{"region":"US","year":2017,"indication":"Newly diagnosed and relapsed CD33+ AML"}],"mechanismSteps":["Antibody binds CD33 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","Calicheamicin is released inside the cell","DNA is damaged (crosslinks or double-strand breaks)","Tumour cell dies by apoptosis"],"dosing":{"route":"IV infusion","schedule":"Newly diagnosed AML: 3 mg/m² (max 4.5 mg) on days 1, 4, 7 of induction with daunorubicin/cytarabine; relapsed: 3 mg/m² days 1, 4, 7 as single agent","modifications":"Hold for hepatotoxicity; veno-occlusive disease risk, especially around transplant","monitoring":"LFTs before each dose, signs of VOD, blood counts","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Haemorrhage"},{"event":"Infection"},{"event":"Hepatotoxicity including veno-occlusive disease"},{"event":"Thrombocytopenia"},{"event":"Infusion reactions"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2000-05-17","type":"accelerated-approval","region":"US","note":"Accelerated approval, relapsed CD33+ AML in older patients; first ADC ever approved","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"For patients with CD33+ AML in first relapse 60 years of age or older and not candidates for cytotoxic chemotherapy"},{"date":"2010-06-21","type":"withdrawal","region":"US","note":"Voluntary withdrawal after confirmatory trial showed no benefit and excess deaths","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2011-11-28","type":"withdrawal","region":"US","note":"Withdrawn: the indication came off the label 11.5 years after its accelerated approval.","indication":"For patients with CD33+ AML in first relapse 60 years of age or older and not candidates for cytotoxic chemotherapy"},{"date":"2017-09-01","type":"approval","region":"US","note":"Re-approval at lower fractionated dose for newly diagnosed and relapsed CD33+ AML (ALFA-0701)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/gemtuzumab-ozogamicin/","neighbours":{"biomarker":[{"id":"cd33-expression","kind":"biomarker","name":"CD33 expression (CD33-positive)","route":"/biomarkers/cd33-expression/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"apl","kind":"cancer","name":"Acute promyelocytic leukaemia","route":"/cancers/apl/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd33","kind":"target","name":"CD33","route":"/targets/cd33/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"term":[{"id":"hydrazone","kind":"term","name":"Acid-labile hydrazone (AcBut)","route":"/terms/hydrazone/"},{"id":"calicheamicin","kind":"term","name":"Calicheamicin","route":"/terms/calicheamicin/"},{"id":"dna-cleaver-payloads","kind":"term","name":"DNA cleaver payloads (enediynes)","route":"/terms/dna-cleaver-payloads/"}],"trial":[{"id":"nct04293562","kind":"trial","name":"A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations","route":"/trials/nct04293562/"},{"id":"alfa-0701","kind":"trial","name":"ALFA-0701","route":"/trials/alfa-0701/"},{"id":"aaml0531","kind":"trial","name":"COG AAML0531","route":"/trials/aaml0531/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}],"paper":[{"id":"paper-aaml0531-gemtuzumab-gamis-jco-2014","kind":"paper","name":"AAML0531: gemtuzumab ozogamicin added to chemotherapy for children and adolescents with acute myeloid leukaemia","route":"/key-papers/paper-aaml0531-gemtuzumab-gamis-jco-2014/"}]}}