Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study

• Published in: Leukemia Vol. 35; no. 5; pp. 1291 - 1300
• Main Authors: Largeaud, Laetitia, Cornillet-Lefebvre, Pascale, Hamel, Jean-François, Dumas, Pierre-Yves, Prade, Naïs, Dufrechou, Stéphanie, Plenecassagnes, Julien, Luquet, Isabelle, Blanchet, Odile, Banos, Anne, Béné, Marie C., Bernard, Marc, Bertoli, Sarah, Bonmati, Caroline, Fornecker, Luc Matthieu, Guièze, Romain, Haddaoui, Lamya, Hunault, Mathilde, Ianotto, Jean Christophe, Jourdan, Eric, Ojeda, Mario, Peterlin, Pierre, Vey, Norbert, Zerazhi, Hacene, Yosr, Hicheri, Mineur, Ariane, Cahn, Jean-Yves, Ifrah, Norbert, Récher, Christian, Pigneux, Arnaud, Delabesse, Eric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2021; Nature Publishing Group; Springer Nature
• Subjects: 692/308/575; 692/699/1541/1990/283/1897; Aged patients; Cancer; Cancer Research; Chemotherapy; Chromosome aberrations; Classification; Critical Care Medicine; Cytarabine; Cytogenetics; Dosage and administration; Drug therapy; Genes; Hematology; Intensive; Internal Medicine; Karyotypes; Leukemia; Life Sciences; Lomustine; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Oncology, Experimental; p53 Protein; Patient outcomes; Pharmacogenetics; Prognosis; Risk assessment; Runx1 protein; Subgroups; Target recognition; Therapeutic targets; France
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-020-01031-1

We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. NPM1 , FLT3 , and DNMT3A were the most frequently mutated genes. A putative therapeutic target was identified in 178 patients (54%). Among five molecular classifications analyzed, the ELN2017 risk classification has the stronger association with the clinical evolution. Patients not treated with lomustine have an expected survival prognosis in agreement with this classification regarding the overall and event-free survivals. In strong contrast, lomustine erased the ELN2017 classification prognosis. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1 , TP53 , and FLT3 -ITD high / NPM1 WT mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.