Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report

ABSTRACT

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

KEYWORDS:

• Large cell neuroendocrine carcinoma (LCNEC)
• immune checkpoint inhibitors (ICIs)
• retreatment with immunotherapy
• hyperprogressive disease (HPD)
• genetic characterization

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

L Shou participated in the clinical management of the patient and conception and edited the manuscript. Q Shu participated in the clinical management of the patient and provided the funding. Y Zhang participated in the clinical management of the patient, manuscript writing, and revision. J Yang contributed to the literature review and illustration. T Shao contributed to the literature review and illustration. J Chen contributed to the illustration. All authors reviewed the manuscript.

Data availability statement

Data sharing is not applicable to this article.

Informed consent statement

Informed consent was obtained from the subject involved in the study.

Institutional review board statement

This study was conducted in accordance with the principles of the Declaration of Helsinki and the Patient provided written informed consent. IRB approval is not required at our institution for case reports.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2313281.

Additional information

Funding

This work was supported by the Projects of Department of Science and Technology of National Administration of Traditional Chinese Medicine and Administration of Traditional Chinese Medicine of Zhejiang Province (GZY-ZJ-KJ-23012).