gemtuzumab ozogamicin
Sources réglementaires consultées
Indications approuvées
- Leucémie aiguë myéloïde CD33 positive nouvellement diagnostiquée chez l’adulte et l’enfant à partir de 1 mois.
- Leucémie aiguë myéloïde CD33 positive récidivante ou réfractaire chez l’adulte et l’enfant à partir de 2 ans.
Contre-indications
Absolues
- Hypersensibilité au gemtuzumab ozogamicine ou à l’un de ses composants.
Mises en garde cliniques
- Mise en garde encadrée · Il peut provoquer une hépatotoxicité et une maladie veino-occlusive hépatique ou un syndrome d’obstruction sinusoïdale sévère ou mortel. Contrôler le bilan hépatique avant chaque dose et les signes tels qu’hépatomégalie, prise de poids rapide et ascite ; arrêter en cas de maladie veino-occlusive. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Mise en garde majeure · Il peut provoquer des réactions sévères ou mortelles à la perfusion, dont l’anaphylaxie. Prémédiquer, surveiller les constantes pendant et au moins 1 heure après, et interrompre immédiatement en cas de réaction ; arrêter définitivement en cas d’anaphylaxie, de symptômes respiratoires sévères ou d’hypotension cliniquement significative. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Mise en garde majeure · La thrombopénie prolongée peut entraîner une hémorragie sévère ou mortelle. Contrôler l’hémogramme avant chaque dose et fréquemment jusqu’à résolution des cytopénies. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Mise en garde majeure · Surveiller l’ECG et les électrolytes en cas de prédisposition à l’allongement du QT ou de prise concomitante de médicaments qui allongent le QT. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
- Mise en garde majeure · Dans la LAM de novo nouvellement diagnostiquée avec cytogénétique à risque défavorable, l’ajout de MYLOTARG à la daunorubicine et à la cytarabine n’a pas amélioré la survie sans événement. Dès que les résultats cytogénétiques sont disponibles, réévaluer individuellement si le bénéfice de la poursuite l’emporte sur le risque. — DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05
Interactions médicamenteuses
- SévèreMédicaments allongeant le QT
Mécanisme: Ils peuvent augmenter le risque d’allongement du QT et d’arythmies.
Recommandation: Si l’association est nécessaire, corriger les électrolytes et surveiller l’ECG au départ et pendant le traitement.
DailyMed, MYLOTARG set_id 32fd2bb2-1cfa-4250-feb8-d7956c794e05https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32fd2bb2-1cfa-4250-feb8-d7956c794e05
Effets indésirables
Communs (≥1%)
hémorragie · infection · fièvre · nausées · vomissements · céphalées · augmentation des transaminases · thrombopénie · neutropénie
Rares mais graves
maladie veino-occlusive hépatique mortelle · anaphylaxie · hémorragie intracrânienne ou mortelle · sepsis · syndrome de lyse tumorale
Grossesse et allaitement
Il peut provoquer une toxicité embryofœtale. Utiliser une contraception efficace pendant le traitement et pendant au moins 6 mois après chez les femmes et 3 mois après chez les hommes ayant une partenaire susceptible d’être enceinte. Ne pas allaiter pendant le traitement ni pendant au moins 1 mois après la dernière dose.
Bibliographie récente (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