How effective is immunotherapy for Xeroderma Pigmentosum?

[Anonymous]

How effective is immunotherapy for Xeroderma Pigmentosum patients who develop advanced or metastatic skin cancers?

[Sana Fathima K S]

Immune checkpoint inhibitors (ICIs) particularly anti-PD-1 agents like pembrolizumab and cemiplimab have shown notably strong responses in Xeroderma Pigmentosum-associated cancers. The underlying rationale is that NER deficiency causes tumors to accumulate an extremely high mutational burden (from unrepaired UV damage), and tumors with high mutation loads tend to respond better to checkpoint inhibition because they generate more neoantigens for the immune system to target.

A retrospective multicenter study of 22 XP patients with metastatic or unresectable cancers treated with ICIs found that all 22 patients (100%) showed tumor regression or remission in response to treatment. Encouragingly, the frequency and type of adverse events in these Xeroderma Pigmentosum patients were comparable to those seen in ICI-treated patients in the general population, suggesting the treatment is not disproportionately riskier for Xeroderma Pigmentosum patients despite their underlying DNA repair defect.

For Xeroderma Pigmentosum patients who develop advanced squamous cell carcinoma or melanoma unsuitable for surgery/radiation, ICIs represent a genuinely effective option, rather than just a palliative approach.

Reference:
Fernandez ER, Tamura D, Khan SG, et al. Retrospective study of efficacy and adverse events of immune checkpoint inhibitors in 22 xeroderma pigmentosum patients with metastatic or unresectable cancers. Frontiers in Oncology, 2023. DOI: 10.3389/fonc.2023.1282823. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634243/

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