Medicana Health Group, Precision Oncology Center, 34750 Istanbul, Türkiye.
Division of Cancer Genetics, Department of Basic Oncology, Institute of Oncology, Istanbul University, 34093 Istanbul, Türkiye.
Curr Oncol. 2024 Sep 29;31(10):5838-5849. doi: 10.3390/curroncol31100434.
There is currently no effective treatment strategy for recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts, unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but and frameshift and splice site mutations (no fusion) with a low tumor mutational burden (TMB), microsatellite stable (MSS) and negative programmed death ligand 1 (PD-L1) were observed. We recommended an anti-programmed cell death protein 1 (anti-PD-1) plus anti-Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) combination based on TMB 2-fold greater-than-median TMB in ACC, tumor harboring multiple immunogenic frameshift or splice site mutations, and PD-L1 negativity. Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in "immune-cold" cancer types.
目前，对于复发性/转移性腺样囊性癌（R/M ACC），尚无有效的治疗策略。此外，最近的单药和联合免疫治疗试验在未经选择的 ACC 队列中失败，与非 ACC 涎腺癌不同。基因组分析显示没有可操作的靶点，但存在 和 移码和 剪接位点突变（无 融合），肿瘤突变负担（TMB）低，微卫星稳定（MSS）和程序性死亡配体 1（PD-L1）阴性。我们建议根据 TMB 在 ACC 中大于中位数的 2 倍、肿瘤携带多个免疫原性移码或剪接位点突变以及 PD-L1 阴性，使用抗程序性细胞死亡蛋白 1（抗 PD-1）联合抗细胞毒性 T 淋巴细胞相关蛋白 4（抗 CTLA-4）联合治疗。因此，我们在一名局部复发性泪腺（LG）ACC 和肺转移的放疗（RT）和化疗（CT）难治性患者中实现了完全缓解，该患者接受了个性化免疫治疗联合综合治疗。因此，评估不仅要考虑传统的免疫生物标志物，还要考虑患者特定的参数，特别是在“免疫冷”癌症类型中。
