Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis C Virus Infection

Abstract

Background. The safety of immune checkpoint inhibitors (ICI) in patients with hepatitis C virus infection (HCV) has not been studied in many cancers as these patients were excluded from most ICI trials. This poses a degree of uncertainty when an HCV patient is being considered for ICI in the absence of data to inform potential adverse events (AEs). Methods. Single institution retrospective chart review of patients with active or resolved HCV who were treated with ICI for cancer of any type and stage from January 2012-December 2019 with emphasis on AEs rates. Result. We identified 40 patients. Males 30 and females 10. Median age 64 years. Cancer types; non-small cell lung cancer 18 (45%), hepatocellular carcinoma 12 (30%), head and neck cancer 4(10%), small cell lung cancer 3 (7.5%), renal cell carcinoma 1 (2.5%), colon cancer 1 (2.5%), and melanoma 1 (2.5%). Hepatitis C was untreated in 17 (42.5%), treated in 14 (35%), and spontaneously resolved in 9 (22.5%). AEs observed were; grade 3 pneumonitis in one patient (2.5%) on pembrolizumab, grade 3 colitis in one patient (2.5%) on nivolumab, two patients with hepatotoxicity (5%) on nivolumab; one patient with grade 1 and the other had grade 2, grade 1-2 fatigue in 3 patients (7.5%), and one patient with hypothyroidism (2.5%). Conclusion. Adverse events rates in untreated and resolved HCV patients treated with ICI for a variety of cancers were comparable to AEs rates reported in clinical trials for patients without HCV. The Oncologist 2021;9999:• • Implications for Practice: The safety of immune checkpoint inhibitors (ICI) in cancer patients with hepatitis C virus infection is a major concern due to the lack of prospective safety data for most cancers. HCV is prevalent worldwide, and the occurrence of cancer where ICI is indicated is not uncommon. We retrospectively reviewed all HCV patients who received ICI for a variety of cancers in our institution over eight years, and the results are presented in this article. The results may help inform clinical decisions and the design of future clinical trials.

Role of CTLA-4, PD-1 and PD-L1 immune biomarkers among HCV patients undergoing hemodialysis

“…In this study, a highly statistical significance difference was observed between the serum levels of the studied biomarkers among participants in the three groups, with a P value <0.001 for all the markers. The significant use of these biomarkers was proved to be efficient not only among ESRD patients (19) and HCV infected patients (7), but also to other diseases/medical conditions, including melanoma (9), sepsis (10) and viral infections including COVID-19 (11). Immune checkpoints have been demonstrated to be utilized in the immune escape of HCV, causing T-cell dysfunction, and the expression of these molecules on suppressor cells, thereby causing difficulties in excluding such infections (20).…”

“…Immune checkpoints operate as immunological regulators. They play a significant part in the process of self-tolerance, which stops the immune system from arbitrarily attacking cells and stops autoimmune reactions to proteins found in the body's own tissues (6) .The most important and widely studied immune biomarkers are Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), Programmed death-1 (PD-1) and Programmed death-ligand-1 (PD-L1), also known as CD152, CD279 and CD274 protein receptors respectively (7). The expression of these immune checkpoints helps in limiting T-cell proliferation, restoring immunological function in the microenvironment of tumors, and regulating responses to self-proteins.…”

Case Report: Pulmonary sarcomatoid carcinoma complicating TP53 mutation treated successfully with Tislelizumab combined with Anlotinib—a case report

“…There are few studies on the effect of HCV on the treatment of ICI, and the reactivation of HCV during ICI treatment is rare (Pertejo-Fernandez et al, 2020;Alkrekshi and Tamaskar, 2021).…”

“…The liver injury was relieved after prednisone treatment, and the subsequent use of Nivolumab was not affected (Alkrekshi and Tamaskar, 2021). Therefore, in patients with chemotherapy and immunotherapy, attention should be paid to the reexamination of HBV-DNA and HCV-RNA when liver injury occurs (Gomes et al, 2020).…”

Safety and efficacy of immune checkpoint inhibitors in patients with cancer and viral hepatitis: The MD Anderson Cancer Center experience

“…In general, the AE pro le was comparable to the published data in non-HCV patients. There were no deaths as a complication of ICIs 7 .…”