Retrospective study of efficacy and adverse events of immune checkpoint inhibitors in 22 xeroderma pigmentosum patients with metastatic or unresectable cancers

Frontiers in Oncology

Oncology

Deborah Tamura¹  Sikandar G. Khan¹  John J. DiGiovanna¹  Kenneth H. Kraemer¹  Elvelyn R. Fernandez¹  Sophie Momen²  Hiva Fassihi²  Robert Sarkany² 

[1] 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;

关键词: xeroderma pigmentation;    cancer;    immune checkpoint inhibitor (ICI);    genodermatosis;    UV radiation;    melanoma;    squamous cell carcinoma;    immunotherapy;   

DOI  :  10.3389/fonc.2023.1282823

 received in 2023-08-24, accepted in 2023-10-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundXeroderma 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.MethodsIn 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.ResultsMetastatic 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.ConclusionIn 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.

【 授权许可】

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Copyright © 2023 Fernandez, Tamura, Khan, Momen, Fassihi, Sarkany, DiGiovanna and Kraemer