Abstract
Simple SummaryThe study objective was to determine if an SNP (single nucleotide polymorphism)-based immune multi-gene panel has the ability to predict adjuvant BCG (Bacillus Calmette–Guérin) immunotherapy responsiveness post-tumor resection in AJCC (American Joint Committee on Cancer) stages III and IV metastatic melanoma patients. A pilot study followed by further verification and control melanoma patient cohorts involving three phase III multicenter clinical trials was used to verify if an immune gene SNP panel could identify if adjuvant BCG therapy correlates with disease outcomes. We found a specific immune gene SNP panel that could identify which patients would respond to adjuvant BCG immunotherapy, but it was not applicable in the control non-immunotherapy treated patients. These studies provide evidence that SNP immune-gene assessment has utility in predicting melanoma patient’s immunotherapy responses to adjuvant BCG immunotherapy.Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and AJCC stage III patients that are sentinel lymph node (SLN) positive receiving no immunotherapy (control cohort; n = 80). The SNP panel analysis demonstrated that the responder patient group had an improved disease-free survival (DFS) (hazard ratio [HR] 1.84, 95% CI 1.09–3.13, p = 0.021) in the pilot cohort. In the verification cohort, an improved overall survival (OS) (HR 1.67, 95% CI 1.07–2.67, p = 0.025) was observed. No significant differences of SNPs were observed in DFS or OS in the control patient cohort. This study demonstrates that SNP immune genes can be utilized as a predictive tool for identifying melanoma patients that are inherently responsive to BCG and potentially other immunotherapies in the future.
Highlights
Melanoma is an antigenic cancer, whereby activated host anti-tumor immunity has been shown to control tumor progression
We developed an immunologic panel of 26 single nucleotide polymorphisms (SNPs) that included cytokines, chemokines, macrophage/monocyte activation markers, dendritic cells marker, and toll-like receptors (TLRs) to assess their ability to predict patients’ responses to adjuvant
The study involved 441 metastatic melanoma patients.The pilot cohort consists of stage IV BCG-treated patients (n = 92) from the JWCI Multicenter Malignant Melanoma
Summary
Melanoma is an antigenic cancer, whereby activated host anti-tumor immunity has been shown to control tumor progression. Immunotherapy in post-surgical, disease-free AJCC (American Joint Committee on Cancer) stage III and IV patients [1,2,3,4]. Newer immunotherapies using monoclonal antibodies, such as ICIs, which target against CTLA-4, PD-1, or PD-L1 [5,6,7], have improved overall survival time when used as both adjuvant and neo-adjuvant therapies in AJCC stage III/IV melanoma patients [8,9,10,11]. In order to improve disease outcomes and reduce unnecessary treatments, personalized therapy for melanoma patients may be needed using an evidence based approach of these patients’ inherited immune status [12]. To improve the efficacy of immunotherapies, we need to identify patients that will respond prior to treatment.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
