Abstract

Objectives: SNPs of CTLA-4 have been shown to be important risk factors associated with autoimmune disease and malignancy , the objectives of this study were to explore the association of CTLA-4 SNPs with the development of myeloma and to evaluate the outcome of patients receiving bortezomib-based regimens in relation to CTLA-4 SNPs.

Methods: Peripheral blood samples from 86 MM patients and 154 controls were obtained for the investigation of CTLA4 polymorphisms, The five SNP genotypes of CTLA-4, namely, -1772(rs733618),-1661 (rs4553808), -318 (rs5742909), CT60 (rs3087243), and +49 (rs231775), were determined by TaqMan SNP genotyping assays (Applied Biosystems) ,

Results: Some of the CTLA-4 polymorphisms display frequencies that are different among the different ethnic groups. The Kaplan-Meier analysis revealed that patients with rs733618 GG showed a significantly lower DFS (0% vs. 57.4%, P = 0.020) and OS (46.3% vs. 83.3%, P = 0.026) than those with GA+AA in MM patients after Botizomib based therapy. Multivariate analyses showed that rs733618 GG were risk factor for OS (HR= 0.025; 95% CI= 0.004-0.161;P=0.000). The incidence of nonhematologic grade 3/4 adverse events was significantly increased in the rs 4553808 GA+GG group compared to AA group(P=0.036).

Conclusion: In summary, CTLA-4 rs733618 GG reduced the progression-free survival and overall survival in MM patients after Botizomib based therapy,knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for MM therapy. The exact effect of the CTLA-4 polymorphism and haplotype on MM therapy outcome should be determined in different cohorts with substantially larger number of subjects.

Correspondence: Professor X-J Huang, Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Sciences, 11 Xizhimen South Street, Beijing 100044, P.R. China. E-mail: huangxiaojun@bjmu.edu.cn

The first 2 authors contributed equally to this work.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.