Time to add gemtuzumab ozogamicin to intensive chemotherapy for NPM1-mutated acute myeloid leukaemia?
Mené en Allemagne et en Autriche sur 588 patients atteints d'une leucémie myéloïde aiguë présentant une mutation au niveau du gène NPM1 et récemment diagnostiquée, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans événement et de la survie globale, et la toxicité de l'ajout de gemtuzumab ozogamicine (un conjugué anticorps-médicament anti-CD33) à une chimiothérapie intensive
Perhaps no other drug in malignant haematology has had such a convoluted clinical development pathway as gemtuzumab ozogamicin, an antibody–drug conjugate targeting CD33. Gemtuzumab ozogamicin was approved 23 years ago for relapsed acute myeloid leukaemia, before being voluntarily withdrawn. Subsequent randomised controlled trials and one meta-analysis showed a survival advantage combining gemtuzumab ozogamicin with intensive chemotherapy for individuals with a favourable, and to a lesser degree intermediate, cytogenetic risk, and subsequently gemtuzumab ozogamicin became an important component of frontline treatment. However, even after 2 decades of investigation, the optimal dosing and patient population is uncertain, and there is substantial variation in use worldwide. A particular area of disagreement is whether gemtuzumab ozogamicin should be administered to all individuals with intermediate risk cytogenetics, or if the benefit is present in a particular subgroup: here the prime suspect has been a large subset with a NPM1 mutation, characterised by a high CD33 expression.
The Lancet Haematology , commentaire, 2022