Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients.
Fiche publication
Date publication
avril 2009
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BORG Christophe, Pr GHIRINGHELLI François
Tous les auteurs :
Ménard C, Blay JY, Borg C, Michiels S, Ghiringhelli F, Robert C, Nonn C, Chaput N, Taïeb J, Delahaye NF, Flament C, Emile JF, Le Cesne A, Zitvogel L
Lien Pubmed
Résumé
Clinical outcomes of gastrointestinal stromal tumor (GIST)-bearing patients treated with imatinib mesylate (IM) are variable. Other than the site of mutation within the c-kit gene, prognostic features of GIST remain undefined. IM can exhibit off-target effects such as triggering natural killer (NK) cell activity. We addressed whether NK cell functions could predict long term survival with IM. NK cell functions were followed up in 77 GIST patients enrolled onto two phase III trials. "Immunologic responders" were defined as patients whose NK cell IFN-gamma values after 2 months of IM were higher than or equal to the baseline value at entry into the trial. The prognostic effect of IFN-gamma on progression-free survival was assessed by a Wald test in a Cox regression analysis using the landmark method and stratified by trial and on the c-kit mutational status. Fifty-six patients were evaluable for the NK cell IFN-gamma responses at baseline and 2 months. Their median follow-up for progression-free survival was 3.7 years. Thirty-four of 56 patients were immunologic responders to IM. In the Cox regression analysis, immunologic responders possessed a hazard ratio of progression or death equal to 0.29 (95% confidence interval, 0.12-0.70; P = 0.006) compared with nonresponders. Kaplan-Meier 2-year survival estimates were 85% for immunologic responders and 50% for nonresponders. Moreover, the immunologic response added prognostic value to the c-kit mutation. The NK cell IFN-gamma production after 2 months of treatment could be considered an independent predictor of long term survival in advanced GISTs treated with IM.
Mots clés
Antineoplastic Agents, therapeutic use, Benzamides, Dendritic Cells, immunology, Exons, Female, Gastrointestinal Stromal Tumors, drug therapy, Humans, Imatinib Mesylate, Interferon-gamma, immunology, Interleukin-2, pharmacology, Killer Cells, Natural, drug effects, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily K, immunology, Natural Cytotoxicity Triggering Receptor 3, immunology, Piperazines, therapeutic use, Proto-Oncogene Proteins c-kit, genetics, Pyrimidines, therapeutic use
Référence
Cancer Res.. 2009 Apr;69(8):3563-9