Immune checkpoint inhibitors (ICI) targeting PD-1, PD-L1, and CTLA-4 have become key treatments for many advanced cancers due to their ability to induce durable responses and prolong survival. Patients with human immunodeficiency virus (HIV) infection are at increased risk of developing cancer, such as lung cancer, head and neck cancer, anal cancer, and Hodgkin lymphoma, but little is known about the efficacy of ICI in these patients, as they were usually excluded from clinical trials of immunotherapies. In a recent systematic review, the authors evaluated outcomes for 73 patients with HIV infection and advanced cancer who were treated with ICI.
Non-small cell lung cancer (NSCLC) (34.2%), melanoma (21.9%), and Kaposi sarcoma (12.3%) were the most common tumor types in these patients. Almost all (95%) were on antiretroviral therapy (ART) at the time of initiation of ICI. The majority of patients (84.9%) received single-agent PD-1 inhibitors, while 6 patients received a CTLA-4 inhibitor (ipilimumab) alone and 5 received ipilimumab in combination or sequence with the PD-1 inhibitor nivolumab. Responses were documented in 45 patients (61.6%) and most of the responding patients were previously treated with systemic therapy. Objective response rate (ORR) varied by tumor type and was 30% in patients with NSCLC, 27% in patients with melanoma, and 63% in patients with Kaposi sarcoma.
The adverse events (AEs) profile was consistent with the known toxicity profiles of these agents, and no new safety signals were seen in patients with HIV infection. Grade 3 or higher immune-related (ir)AEs occurred in of patients and included insulin-dependent diabetes, colitis, myositis, and hepatitis. Of the 6 patients who experienced grade ³3 irAEs, 4 were being treated with an ipilimumab-containing regimen.
Paired pre- and posttreatment HIV loads were available for 34 patients. Twenty-eight patients had undetectable HIV loads at baseline, and viral loads remained suppressed in all but 2 (93%) of these patients. Among the 25 patients with paired pre- and posttreatment CD4 T cell levels, 14 (56%) experienced an increase in CD4 T cells, while 11 (44%) experienced a decrease. The mean change in CD4 count following ICI treatment was 12.3 cells/mL.
The authors concluded that ICIs are a safe and effective therapy for HIV-infected patients with advanced cancer and should be considered as a treatment option in these patients. Ongoing prospective trials are further evaluating the role of ICI in patients with HIV infection.