Safety and efficacy of anti-PD-1 therapy for metastatic melanoma and non-small-cell lung cancer in patients with viral hepatitis: a case series

Abstract

Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC). We describe seven patients treated with PD-1 inhibitors nivolumab and pembrolizumab for either metastatic melanoma or metastatic NSCLC in the setting of chronic or past HBV/HCV infection. The safety and efficacy of treatment were analysed retrospectively by examining response to treatment, alanine transaminase (ALT) trends and viral load trends. One patient showed an increase in ALT of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 severity that returned to the normal range following treatment of his HCV infection with ledipasvir 90 mg/sofosbuvir 400 mg. An additional four patients showed an increase in ALT of CTCAE grade 1 severity. The remaining two patients experienced no hepatic toxicity, with stable disease continuing after more than 24 cycles of nivolumab. Efficacy was similar to the data of published trials. Our results indicate that patients with metastatic melanoma and NSCLC can be treated safely with PD-1 inhibitors in the context of HBV/HCV infection. However, we recommend that those with active viral hepatitis be monitored closely in consultation with a hepatologist and treated with antiviral therapy if indicated.

PD‐1 inhibitors for non‐small cell lung cancer patients with special issues: Real‐world evidence

“…In another study, anti‐PD‐1 therapy induced disease flares in 38% of melanoma patients with autoimmune disease, and 12% of patients discontinued ICI treatment because of underlying disease flares or irAEs . Another study investigating anti‐PD‐1 therapy for seven melanoma or NSCLC patients with viral hepatitis revealed that one HCV patient experienced grade 2 ALT elevation and four patients experienced grade 1 ALT elevation . Regarding ILD, a case series indicated that anti‐PD‐1‐related pneumonitis occurred more frequently in NSCLC patients with ILD than in those without (31% vs 12%, P = .014) .…”

Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections

“…For patients who have positive screening test results, chest imaging may be performed. Further evaluation for TB may be carried out for patients with abnormal chest imaging results. Recent studies indicate that PD‐1/PD‐L1 inhibitors do not show increased toxicity in patients with tumor in the context of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection . However, for patients developing irAEs, treatment with immunosuppressive therapy may increase the risk of reactivation of HBV/HCV infection.…”

“…26 Therefore, further studies are needed to investigate the relationship between PD-1/PD-L1 blockage and infection. 27,28 However, for patients developing irAEs, treatment with immunosuppressive therapy may increase the risk of reactivation of HBV/HCV infection. Furthermore, for patients without irAEs or treatment with immunosuppressants, there is a possibility of reactivation of latent/chronic infections following immune checkpoint inhibitor therapy.…”

Simultaneous targeted therapy for metastatic melanoma and hepatitis C

“…Good safety profiles for patients with hepatitis C have already been reported for anti-PD-1 therapy [12,13]. Therefore, careful clinical examination and a detailed anamnesis is of great importance.…”

“…Therefore, careful clinical examination and a detailed anamnesis is of great importance. Good safety profiles for patients with hepatitis C have already been reported for anti-PD-1 therapy [12,13]. Serial application of the anti-PD-1 mAb nivolumab and ledipasvir has also been described in a patient with advanced melanoma and hepatitis C [14].…”