gemtuzumab ozogamicin
Regulatory sources consulted
Approved indications
- Newly diagnosed CD33-positive acute myeloid leukemia in adults and pediatric patients aged 1 month and older.
- Relapsed or refractory CD33-positive acute myeloid leukemia in adults and pediatric patients aged 2 years and older.
Contraindications
Absolute
- Hypersensitivity to gemtuzumab ozogamicin or any component.
Clinical warnings
- Boxed warning · It can cause hepatotoxicity and severe or fatal hepatic veno-occlusive disease or sinusoidal obstruction syndrome. Check liver tests before each dose and signs such as hepatomegaly, rapid weight gain, and ascites; discontinue for veno-occlusive disease. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Major warning · It can cause severe or fatal infusion reactions, including anaphylaxis. Premedicate, monitor vital signs during and for at least 1 hour afterward, and immediately interrupt for a reaction; permanently discontinue for anaphylaxis, severe respiratory symptoms, or clinically significant hypotension. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Major warning · Prolonged thrombocytopenia can cause severe or fatal hemorrhage. Check blood counts before each dose and frequently until cytopenias resolve. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Major warning · Monitor ECG and electrolytes in patients predisposed to QT prolongation or receiving concomitant QT-prolonging medicines. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Major warning · In newly diagnosed de novo AML with adverse-risk cytogenetics, adding MYLOTARG to daunorubicin and cytarabine did not improve event-free survival. Once cytogenetic results are available, reassess individually whether the benefit of continuing outweighs the risk. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
Drug interactions
- HighQT-prolonging medicines
Mechanism: They can increase the risk of QT prolongation and arrhythmias.
Recommendation: If the combination is needed, correct electrolytes and monitor ECG at baseline and during treatment.
DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32fd2bb2-1cfa-4250-feb8-d7956c794e05
Adverse events
Common (≥1%)
hemorrhage · infection · fever · nausea · vomiting · headache · increased transaminases · thrombocytopenia · neutropenia
Rare but serious
fatal hepatic veno-occlusive disease · anaphylaxis · intracranial or fatal hemorrhage · sepsis · tumor lysis syndrome
Pregnancy and lactation
It can cause embryo-fetal harm. Use effective contraception during treatment and for at least 6 months afterward in females and 3 months afterward in males with partners who can become pregnant. Do not breastfeed during treatment or for at least 1 month after the last dose.
Recent literature (PubMed)
The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.
Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as "biological missiles", is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.
The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions. Gemtuzumab ozogamicin is a humanized monoclonal antibody conjugate that is used in the therapy of acute myelogenous leukemia. Gemtuzumab ozogamicin has been linked to transient serum enzyme elevations during therapy and not uncommon instances of acute sinusoidal obstruction syndrome, which can be severe and even fatal. No information is available on the clinical use of gemtuzumab ozogamicin during breastfeeding. Because gemtuzumab is a large protein molecule with a molecular weight of about 152,000 Da the amount in milk is likely to be very low.[1] It is also likely to be partially de