Fernandez Elvelyn R, Tamura Deborah, Khan Sikandar G, Momen Sophie, Fassihi Hiva, Sarkany Robert, DiGiovanna John J, Kraemer Kenneth H
DNA Repair Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.
National Xeroderma Pigmentosum Service, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Front Oncol. 2023 Oct 25;13:1282823. doi: 10.3389/fonc.2023.1282823. eCollection 2023.
Xeroderma pigmentosum (XP), a rare disease with defects in DNA repair genes, has >1,000-fold increased risk of ultraviolet-induced skin cancers. Immune checkpoint inhibitors (ICIs) are used for treating cancers with large numbers of mutations but may also promote adverse events (AEs). Deficient DNA repair in XP patients may lead to increased numbers of mutations, leading to enhanced efficacy of cancer response or, alternatively, to increased AE in response to ICI. We sought to compare the efficacy and AE of ICI in XP patients with metastatic or unresectable cancers to that of ICI-treated patients in the general population.
In this retrospective study, we reviewed medical records of XP patients treated in the United States and in London (UK). We also reviewed published reports of ICI-treated XP patients and patients in the general population.
Metastatic or unresectable cancers in all 22 (100%) XP patients showed regression or remission in response to ICI. The types and frequencies of AE in XP patients were similar to those reported among ICI-treated patients in the general population. However, two XP patients had concurrent additional cancers that did not respond to ICI, two XP patients had cancer recurrence or progression after initial response, and eight XP patients developed new skin cancers during or after ICI treatment.
In this retrospective study with small sample size, XP patients demonstrated positive responses to ICI and the treatment was well tolerated but some patients developed new skin cancers while being treated. ICIs can be considered in treating metastatic or unresectable cancers in XP patients.
着色性干皮病（XP）是一种DNA修复基因存在缺陷的罕见疾病，紫外线诱发皮肤癌的风险增加了1000倍以上。免疫检查点抑制剂（ICI）用于治疗具有大量突变的癌症，但也可能引发不良事件（AE）。XP患者的DNA修复缺陷可能导致突变数量增加，从而提高癌症反应的疗效，或者相反，导致对ICI反应时不良事件增加。我们试图比较ICI在患有转移性或不可切除癌症的XP患者中的疗效和不良事件与在普通人群中接受ICI治疗的患者的疗效和不良事件。
在这项回顾性研究中，我们查阅了在美国和伦敦（英国）接受治疗的XP患者的病历。我们还查阅了已发表的关于接受ICI治疗的XP患者和普通人群患者的报告。
所有22例（100%）XP患者的转移性或不可切除癌症对ICI均有消退或缓解。XP患者不良事件的类型和频率与普通人群中接受ICI治疗的患者报告的相似。然而，两名XP患者同时患有对ICI无反应的其他癌症，两名XP患者在初始反应后出现癌症复发或进展，八名XP患者在ICI治疗期间或之后出现新的皮肤癌。
在这项小样本回顾性研究中，XP患者对ICI表现出阳性反应，且治疗耐受性良好，但一些患者在治疗期间出现了新的皮肤癌。可以考虑使用ICI治疗XP患者的转移性或不可切除癌症。
