Personalized Immunotherapy Achieves Complete Response in Metastatic Adenoid Cystic Carcinoma Despite Lack of...

Area of Science:

• Oncology
• Immunotherapy
• Genomics

Background:

• Recurrent/metastatic adenoid cystic carcinoma (R/M ACC) presents a significant unmet clinical need, with limited treatment options.
• Previous immunotherapy trials in unselected ACC cohorts have yielded poor outcomes, contrasting with other salivary gland cancers.

Observation:

• Genomic analysis of ACC revealed specific mutations (e.g., NOTCH1, KDM6A, CTCF) but lacked actionable targets and showed low tumor mutational burden (TMB), microsatellite stability (MSS), and PD-L1 negativity.
• A patient with R/M ACC refractory to radiotherapy (RT) and chemotherapy (CT) exhibited a TMB twice the median, multiple immunogenic mutations, and PD-L1 negativity.

Findings:

• A personalized immunotherapy regimen, combining anti-programmed cell death protein 1 (anti-PD-1) and anti-Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), was administered.
• This combination therapy, alongside integrative therapeutics, resulted in a complete response in the refractory R/M ACC patient with lacrimal gland (LG) involvement and lung metastasis.

Implications:

• The findings underscore the importance of assessing patient-specific genomic and immune biomarkers beyond conventional markers.
• Tailored immunotherapy strategies, considering factors like TMB and specific mutation profiles, may offer new hope for "immune-cold" tumors like ACC.
• Integrative therapeutic approaches combined with personalized immunotherapy show promise for challenging R/M ACC cases.