Herpes Zoster Following Chemo-Immunotherapy With Pembrolizumab in Metastatic Non-small Cell Lung Cancer: A Case...

Chemo-immunotherapy has reshaped the treatment of metastatic non-small cell lung cancer (NSCLC), yet data on varicella-zoster virus (VZV) reactivation under these regimens are limited. Major immunotherapy trials do not specifically describe herpes zoster events in patients receiving combined chemotherapy and immune checkpoint inhibitors.

We describe a case of metastatic lung adenocarcinoma (ADC) treated with first‑line Pemetrexed-Carboplatin-Pembrolizumab plus Denosumab in which herpes zoster occurred during treatment, detailing clinical course, management, and outcomes.

We report a 64-year-old former smoker with metastatic lung ADC involving lymph nodes and bone, Programmed Cell Death Protein Ligand (PD-L1) expression 0%, and no actionable oncogenic alterations. He was treated with first-line Pemetrexed-Carboplatin-Pembrolizumab plus Denosumab. Treatment was well tolerated, and post-cycle 4 imaging showed stable disease according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. Approximately four months after initiation of chemo-immunotherapy, he developed a painful, unilateral, dermatomal vesicular eruption over the right lower thorax, clinically consistent with herpes zoster. The diagnosis of herpes zoster was clinical rather than microbiological. Systemic anticancer therapy was temporarily suspended. The patient received oral Acyclovir, step II analgesics, and local wound care for 14 days. Complete resolution of skin lesions and pain occurred within three weeks, without zoster-related complications. Maintenance Pemetrexed-Pembrolizumab-Denosumab was then resumed, with sustained tumor control and no recurrence of herpes zoster during follow-up.

This case illustrates herpes zoster reactivation during Pembrolizumab-based chemo-immunotherapy in metastatic NSCLC. It emphasizes the importance of systematically excluding infectious causes in new cutaneous eruptions under immunotherapy and supports multidisciplinary management. These findings also highlight the need to further explore VZV screening and vaccination strategies in cancer patients undergoing immunosuppressive treatments.