In a retrospective serieson patients with HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) who were treated with immune hceckpoint inhibitors (ICI), researchers found similar toxicity and efficacy rates among patients without chronic viral infections. The findings support the inclusion of these patient populations in ICI-based clinical trials and treatments.

ICI therapy is a form of cancer immunotherapy that suppresses immune inhibitory pathways. In patients with cancer, ICI therapy has been found to improve survival compared with chemotherapy treatment alone, and is now considered standard of care.

The authors noted that there are limited data on the safety and efficacy of ICI therapy in patients with chronic viral infections and advanced-stage cancer because the majority of early ICI clinical trials exclude patients with chronic viral infections due to concerns about viral reactivation, toxicity, and efficacy in these populations.

The study authors used the REDCap based immuno-oncology database at MedStar Health Hospitals along with pharmacy records to identify real world data and to identify patients treated with ICI therapies either as a single agent, in combination with other ICIs, or with chemotherapy-targeted therapy.

They identified 50 patients with HIV, HBV, and HCV comorbidities. The median age of patients in both the HIV and HBV/HCV cohorts was 62 years, and the majority of patients were treated with anti-programmed cell death ligand 1 (PD-L1) monotherapy.

Safety Findings
Among the HIV cohort, the incidence of immune-related adverse events (irAEs) of any grade was 24%, and the incidence of irAEs of grade 3 or higher was 14%. Among the 5 patients with HIV who developed irAEs, 1 had low CD4-positive T-cell counts during ICI treatment. The authors noted that the risk of irAEs did not seem to increase with the addition of chemotherapy to anti-PD-L1 therapy.

Similarly, in the combination HCV/HBV cohort, any grade irAEs were found in 44% of patients, and grade 3 or higher irAEs were found in 29%. Specifically, 12% of patients were diagnosed with colitis, 18% with rash/pruritus, 18% with hepatitis, 6% with pneumonitis, 6% with hypothyroidism, and 1 patient with diabetes mellitus and encephalitis. No HBV viral reactivation or changes in HBV medications were observed in any of the patients.

Efficacy Findings
Among the 21 patients with HIV, pre-treatment HIV viral load was available in 15 patients, 6 of whom had an HIV viral load within 1 month of ICI initiation. Among those 6, only 5 had both pre- and post-treatment HIV viral loads. Of these patients, 2 maintained undetectable levels, 1 patient's viral load increased from 0 to 80 copies/mL, and 2 patients' viral loads decreased. The authors stated that in the 2 patients whose viral loads decreased, it was noted that they became more compliant to their HIV treatment.

Similarly, in the 23 patients with HCV (18 with HCV and 5 with HBV/HCV), 9 patients were successfully treated for their infection, 9 others were untreated, and 5 patients had unknown treatment status before ICI initiation. Among the 9 untreated patients with HCV, none received HCV treatment concurrently with ICI treatment.

Pre- and post-viral loads were available in 4 patients and HBV viral load remained undetectable in all of them. Nine patients were taking anti-HBV treatment during ICI treatment, and no changes in anti-HBV medication were made during ICI treatment.

Conclusions
Based on these results, the researchers concluded that toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. They argued that ICI therapy could be used in this patient population and that these patients should be included in future trials.

Reference
Shah N, Al-Shbool G, Blackburn M, Cook M, et al. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection. Journal for Immunotherapy of Cancer. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0771-1. Accessed Jan 15, 2020.