Prevalence of and mutations in a real‑life CLL cohort still on ibrutinib after three years: a FILO group study.
Fiche publication
Date publication
juin 2019
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre, Pr FORNECKER Luc-Matthieu, Pr DELMER Alain
Tous les auteurs :
Quinquenel A, Fornecker LM, Letestu R, Ysebaert L, Fleury C, Lazarian G, Dilhuydy MS, Nollet D, Guieze R, Feugier P, Roos-Weil D, Willems L, Michallet AS, Delmer A, Hormigos K, Levy V, Cymbalista F, Baran-Marszak F
Lien Pubmed
Résumé
Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in the Bruton's tyrosine kinase () and/or phospholipase Cg2 () genes. However, mutational information for patients still on ibrutinib is limited. Here, we report a study aimed to provide a 'snapshot' of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least three years of treatment. Of 204 patients who initiated ibrutinib via an early access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after three years and 57 provided a fresh blood sample. Thirty patients had a CLL clone {greater than or equal to}0.5 G/L, enabling next‑generation sequencing (NGS); and mutations were detected in 57% and 13% of the NGS samples, respectively. The presence of a mutation was significantly associated with subsequent CLL progression, at a median 8.5 months from sample collection (=0.0005 versus nomutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a mutation may benefit from an early switch to another treatment.
Référence
Blood. 2019 Jun 26;: