Supplementary Material for: A complete response to combined immunotherapy in a patient with an ATM plus SF3B1 mutation and a moderate tumor mutational burden with a high-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC): Case report and review of the literature

Introduction: High-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC) is a rare subtype of prostate cancer with limited therapeutic options and poor prognosis. Understanding biomarkers that influence the efficacy of immune checkpoint inhibitors (IO) is vital to form a better therapeutic arsenal for these patients. Case presentation: We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The patient was showing signs of a rapid decline in quality of life despite his prostate-specific antigen (PSA) levels remaining undetectable and had no previous response to standard therapies. The results of the next sequencing generation (NGS) DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient . Conclusions: This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.

引言：高级别治疗相关神经内分泌前列腺癌（T-NEPC）是一种罕见的前列腺癌亚型，其治疗选择有限，预后不佳。理解影响免疫检查点抑制剂（IO）疗效的生物标志物对于构建针对此类患者的更优治疗方案至关重要。病例报告：我们描述了一名T-NEPC患者在接受标准治疗方案失败后，对免疫检查点抑制剂联合免疫疗法（伊匹单抗联合尼伏单抗，Ipi/nivo）表现出显著反应的情况。尽管该患者的前列腺特异性抗原（PSA）水平未检测到，且对标准疗法无反应，但生活质量迅速下降。下一代测序（NGS）DNA分析结果显示存在中间肿瘤负荷、ATM突变以及罕见的SF3B1（G742D）突变，这为该患者的IO疗法提供了合理的依据。结论：本案例突出了肿瘤的遗传特征，其中ATM和SF3B1突变呈罕见组合，这些突变可作为T-NEPC及其他肿瘤类型IO疗法的生物标志物进一步研究。