Hyperprogression under Immune Checkpoint Inhibitor: a potential role for germinal immunogenetics - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2020

Hyperprogression under Immune Checkpoint Inhibitor: a potential role for germinal immunogenetics

Résumé

Hyperprogressive disease (HPD), an unexpected acceleration of tumor growth kinetics, is described in cancer patients treated with anti-PD-1/anti-PD-L1 agents. Here, our aim was to take into consideration the host and explore whether single nucleotide polymorphisms (SNPs) in key genes involved in immune response might predispose to HPD. DNA was extracted from blood-samples from 98 patients treated under CPI monotherapy. Four candidate genes (PD-1, PD-L1, IDO1 and VEGFR2) and 15 potential SNPs were selected. The TGKR (ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR≥2. TGKR calculation was feasible for 80 patients (82%). HPD was observed for 11 patients (14%) and was associated with shorter overall survival (P = 0.003). In univariate analysis, HPD was significantly associated with age ≥70 y (P = 0.025), immune-related toxicity (P = 0.016), VEGFR2 rs1870377 A/T or A/A (P = 0.005), PD-L1 rs2282055 G/T or G/G (P = 0.024) and PD-L1 rs2227981 G/A or A/A (P = 0.024). Multivariate analysis confirmed the correlation between HPD and age ≥70 y (P = 0.006), VEGFR2 rs1870377 A/T or A/A (P = 0.007) and PD-L1 rs2282055 G/T or G/G (P = 0.018). Immunogenetics could become integral predictive factors for CPI-based immunotherapy.
Fichier principal
Vignette du fichier
s41598-020-60437-0.pdf (1.14 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

inserm-02497242 , version 1 (03-03-2020)

Identifiants

Citer

Sadal Refae, Jocelyn Gal, Patrick Brest, Damien Giacchero, Delphine Borchiellini, et al.. Hyperprogression under Immune Checkpoint Inhibitor: a potential role for germinal immunogenetics. Scientific Reports, 2020, 10 (1), pp.3565. ⟨10.1038/s41598-020-60437-0⟩. ⟨inserm-02497242⟩
59 Consultations
83 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More