Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Abstract

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.

CD200 genotype is associated with clinical outcome of patients with multiple myeloma

“…Interestingly, we did no find differences in cumulative incidence of progression and PFS as it has been previously described for CTLA4 genetic variants ( 25 ). These findings suggest that the studied genotypes of rs1131199 CD200 are not related with the mechanism of escape of cancer cells from immune surveillance control.…”

“…We analyzed the polymorphisms of CTLA4, BTLA, CD28, PD-1 and LAG-3 genes. Our results showed that the CTLA4 genotype identify patients with earlier progression of MM ( 25 ). Based on these interesting findings we decided explored other immune checkpoint molecule as CD200 in the same population.…”

“…However, few date are available concerning the relevance of immune checkpoint molecules in the kinetics of progression of MM patients. Recently, our group showed that the CTLA4 genotype may be useful to identify MM patients with high risk of progression ( 25 ).…”

Checkpoint inhibition in hematologic malignancies

“…Gonzalez-Montes et al. identified a CTLA-4 polymorphism (CTLA4 rs231775 AA/AG) that served as an independent predictor of progressive disease ( 66 ). They reported that the AA/AG genotype was associated with median PFS of 32 months vs 96 months for the normal GG genotype while 5-year survival rate was half (25% vs 55%, respectively).…”