Does prior treatment with anti-PD 1 immune check point inhibitors (ICIs) mitigate infection with herpes and SARS-CoV-2 viruses: Clinical evidence supporting basic hypotheses.

Abstract

e24045 Background: We present the initial clinical evidence of likely mitigation of viral infections in patients with non-small cell lung cancer (NSCLC) who previously responded to pembrolizumab. This may constitute a late beneficial effect of ICI treatment, and may identify patients with decreased risk for poor outcomes from major viral infections.While prior clinical reports are lacking, there is abundant laboratory evidence that: 1) immune checkpoint inhibition of the PD-1-mediated signaling pathway augments the response of antigen-specific T cells which likely leads to enhanced viral clearance (Dyke, Eur J Clin Immunol 2017); and 2) high levels of PD-1 positive CD-8 T cells have been demonstrated in HIV, Hepatitis B & C infections, akin to the PD-1 positive tumor-reactive tumor infiltrating cells described in host directed mechanisms against cancer (Rao, Int J Inf Dis 2017). Methods: We report the limited pattern and shortened course of three instances of herpetic infection, and one occurrence of SARS-CoV-2, which suggest enhanced mitigation of viral infection in patients previously treated with ICIs. We have seen no other cases of such limited and rapidly clearing herpes in our thoracic oncology practice. Results: Patient characteristics: ages 38 – 78; 1 female; all stage IV extent; 1 with squamous cell carcinoma and the others had adenocarcinoma/sarcomatoid carcinoma NSCLC; PDL-1 tumor proportion scores > 90% except for the 1 patient with squamous cell carcinoma who had a PDL-1 score < 1%. One patient received only pembrolizumab; the others also received cisplatin-based combination chemotherapy. All responded well to anticancer treatment, were off all treatment for > 1 year, and continue to do well 2 – 5 years after diagnosis. Three infections diagnosed as Herpes zoster presented in each case with only one or two vesicles within a single dermatome. Each infection was diagnosed 48 – 72 hours after eruption, was only minimally symptomatic, and cleared within one or two days. The case of documented SARS-CoV-2 occurred in a 60 year old woman with NSCLC and COPD who was off ICI therapy for 3 years with a complete response. She had minimal COVID-19 symptoms which cleared within 3 days. Conclusions: We conclude that: 1) these cases suggest mitigation of viral infections in patients with NSCLC who had prior anticancer benefit with pembrolizumab, and constitute a long term positive effect of ICIs; 2) these results support the pre-clinical findings and hypotheses of enhanced antiviral immune response with ICI agents; and 3) prospective evaluation of large populations of patients with cancer receiving ICIs is warranted to determine if this benefit is reproducible, what proportion of patients benefit, the magnitude of benefit, and to guide in prospective antiviral treatment in the highly vulnerable NSCLC population.