CTLA-4 polymorphisms are associated with treatment outcomes of patients with multiple myeloma receiving bortezomib-based regimens

• Published in: Annals of hematology Vol. 97; no. 3; pp. 485 - 495
• Main Authors: Qin, Xiao-Ying, Lu, Jin, Li, Guo-Xuan, Wen, Lei, Liu, Yang, Xu, Lan-Ping, Chang, Ying-Jun, Liu, Kai-Yan, Jiang, Zheng-Fan, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2018; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Case-Control Studies; CTLA-4 Antigen - genetics; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Hematology; Humans; Inhibitor drugs; Male; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Multiple Myeloma - mortality; Oncology; Original Article; Polymorphism; Polymorphism, Single Nucleotide; Targeted cancer therapy; Treatment Outcome; CTLA-4 polymorphisms; Bortezomib; Nonhematologic adverse events; Survival; Multiple myeloma
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-017-3203-7

Single-nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte antigen-4 (CTLA-4) are important risk factors associated with autoimmune diseases and malignancies. This study explored the association of CTLA-4SNPs with the development of myeloma and evaluated the outcome of patients receiving bortezomib-based regimens in relation to CTLA-4SNPs. Peripheral blood samples from 86 patients with multiple myeloma (MM) and 154 healthy controls were obtained to investigate CTLA4 polymorphisms. Five SNP genotypes of CTLA-4, namely, −1772 (rs733618), −1661 (rs4553808), −318 (rs5742909), CT60 (rs3087243), and +49 (rs231775), were evaluated through TaqMan SNP genotyping assays (Applied Biosystems). Some of the CTLA-4 polymorphisms displayed frequencies that vary among ethnic groups. Kaplan–Meier analysis revealed that patients with rs733618 GG showed a significantly lower disease-free survival (0 vs. 57.4%, P  = 0.020) and overall survival (46.3 vs. 83.3%, P  = 0.026) than those with GA+AA following bortezomib-based therapy. Multivariate analyses showed that rs733618 GG was a risk factor for OS (HR = 0.012; 95% CI = 0.001–0.199; P  = 0.002). The incidence of nonhematologic grade 3/4 adverse events significantly increased in the rs4553808 GG+GA group compared with that in the AA group ( P  = 0.036). CTLA-4 rs733618 GG reduced the progression-free survival and the overall survival of patients with MM who received bortezomib-based therapy. Information regarding CTLA-4 polymorphisms and haplotypes may be used to improve MM therapy. Future studies must determine the precise effect of CTLA-4 polymorphisms and haplotypes on MM therapy outcomes by using different cohorts with a large number of subjects.