The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck

Abstract

Background and Objectives: Adenoid cystic carcinoma (ACC) of the head and neck is generally slow-growing but has a high potential for local recurrence and metastasis to distant organs. There is currently no standard pharmacological treatment for recurrent/metastatic (R/M) ACC, and there are cases in which immune checkpoint inhibitors (ICIs) are administered for ACC according to head and neck squamous cell carcinoma (HNSCC). However, the efficacy of ICIs for ACC remains unclear, and the predictive biomarkers need to be elucidated. Materials and Methods: The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database enabled the retrospective but nationwide analysis of 263 cases of ACC of the head and neck. Then, we examined and reported four cases of ACC that received ICIs and comprehensive genomic profiling (CGP) in our institution. Results: The C-CAT database revealed that 59 cases out of 263 received ICIs, and the best response was 8% of objective response rate (ORR) and 53% of disease control rate (DCR) (complete response, CR 3%, partial response, PR 5%, stable disease, SD 44%, progressive disease, PD 19%, not evaluated, NE 29%). The tumor mutational burden (TMB) in ACC was lower overall compared to HNSCC and could not be useful in predicting the efficacy of ICIs. Some cases with MYB structural variants showed the response to ICIs in the C-CAT database. A patient with MYB fusion/rearrangement variants in our institution showed long-term stable disease. Conclusions: ICI therapy is a potential treatment option, and the MYB structural variant might be a candidate for predictive biomarkers for immunotherapy in patients with R/M ACC.

Keywords: C-CAT database; MYB; adenoid cystic carcinoma; comprehensive genomic profiling test; head and neck; immunotherapy.

Figure 1

The scheme of total population and genetic information in ACC patients from CGP in the C-CAT database. (A) The scheme of the population from the C-CAT database using the F1(F1CDx or F1LCDx) test and NCC Oncopanel test. Information of 53,906 patients was registered in C-CAT, with a total of 263 patients diagnosed with R/M ACC of head and neck. (B) Percentage of the top 10 most frequent genes and variant types by histological type. Color coding indicates the variant type. (C) Percentage of TMB value in 59 patients who received ICI. TMB value is indicated as low (5 Muts/Mb or less), intermediate (6–9 Muts/Mb), and high (10 Muts/Mb or more).

Figure 2

(A) Clinical course. (B) FDG-PET or CT scan before therapy with pembrolizumab, 2 months after treatment, and 17 months since he initiated the ICI therapy. The red color means FDG uptake.