A retrospective study driven by Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, found that cancer patients battling viral infections such as HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) shouldn’t be precluded from immune checkpoint inhibitor (ICI) studies.
AMJC reports that as a matter of practice, patients with chronic viral infections are excluded from ICI therapy, advanced immunotherapy-based treatments that suppress immune inhibitory pathways like programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis and the cytotoxic lymphocytes antigen proteins (CTLA-4) pathway.
The study was recently published in the Journal for ImmunoTherapy of Cancer and represents a retrospective analysis of patients afflicted with advanced-stage cancers and HIV, HBV or HCV infection treated with ICI therapy during stays at 5 MedStar Health hospitals from January 2011 to April 2018.
The retrospective investigators identified 50 patients meeting the inclusion criteria of the study. Sixteen patients lived with HIV, 29 with HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. At a median age of 62 years, most of these patients were treated with anti-PD-(L)1 monotherapy while one was treated with a combination of ipilimumab and nivolumab; another 6 of the patients were treated with anti-PD-(L)1/chemotherapy/targeted therapy combination.
Among the study cohort, the most common cancer diagnoses were non-small cell lung cancer. Among the HBV/HCV cohort, hepatocellular carcinoma was the most prevalent cancer.
The HIV cohort (n = 21) reported immune-related adverse events (irAEs) was 24% with grade ≥ 3 irAEs 14%. For five patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cee counters were observed, reports Sara Karlovitch with AJMC.
Additionally, RECIST evaluable patients (n = 18) had an overall response rate (ORR) of 28% with two complete responses and three partial responses. Ms. Karovitch repots that the responders included two patients with low baseline CD+4 T-cell counts.
The HBV/HCV cohort (n = 34) any grade irAEs equaled 44% including grade ≥ 3 irAEs at 29%. The authors summarized that RECIST confirmed ORR (21% and six partial responses); 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), and there was no evidence of viral reactivation.
Investigators acknowledge that further systematic research is required to validate these findings. They did declare, however, that those with HIV, HBV, or HCV being treated with ICI therapy had similar rates of efficacy and toxicity as to those without such chronic viral infections. Moreover, they found no viral reactivation. And, tumor responses occurred in patients with HIV with low CD4 T-cell counts.
To summarize, although it would appear, at least among this small patient sample, that patients with chronic viral infections undergoing ICI therapy responses are similar to those that are not afflicted with chronic viral infections, and hence support the use of ICI therapy in this patient population in future clinical trials. But additional studies are required for a more systematic and holistic understanding of this patient population.
Research Centers Involved
The following research sites were involved with this observational study.
· MedStar Georgetown University Hospital Lombardi Comprehensive Cancer Center
· Georgetown University Innovation Center for Biomedical Informatics
· Memorial Sloan Kettering Cancer Center
NJ Shah, Lombardi Comprehensive Cancer Center MedStar Georgetown University Hospital
AL-Shbook, Department of Medicine, MedStar Washington Hospital Center,
G. Blackburn, Department of Medicine, MedStar Georgetown University Hospital