Safety and Efficacy of Immune Checkpoint Inhibitor Therapy in Patients With HIV Infection and Advanced-Stage Cancer

Abstract

IMPORTANCEPatients with HIV infection are at increased risk for cancer. Cancer is the leading cause of death among non-AIDS-defining illnesses in these patients. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of cancer. However, clinical trials of ICIs have historically excluded patients with HIV infection. The safety and efficacy profile of ICIs is unknown in this underrepresented population.OBJECTIVE To summarize results on the safety and efficacy of ICI therapy in HIV-infected patients with advanced-stage cancer.EVIDENCE REVIEW This systematic review was conducted in accordance with PRISMA guidelines. A literature search of PubMed was performed on April 16, 2018, using the keyword HIV and the names of ICIs approved by the US Food and Drug Administration (ipilimumab, nivolumab, pembrolizumab, avelumab, atezolizumab, and durvalumab). Patients with HIV infection who were being treated with ICIs for advanced-stage cancer were included. In addition, abstracts and posters from major oncology and AIDS society annual meetings from 2016 through 2018 were reviewed.FINDINGS Seventy-three patients (66 [90.4%] male; mean age, 56.1 years [range, 30.0-77.0 years]) were identified from 13 articles (11 case reports and 2 case series) and 4 meeting abstracts. Sixty-two patients were treated with anti-programmed cell death 1 (anti-PD-1) therapy, 6 with anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) therapy, 4 with anti-PD-1/CTLA-4 therapy, and 1 with sequential ipilimumab and nivolumab therapy. Immune checkpoint inhibitor therapy was generally well tolerated, with grade 3 or higher immune-related adverse events noted in 6 of 70 patients (8.6%). Among 34 patients with known paired pretreatment and posttreatment HIV loads, HIV remained suppressed in 26 of the 28 (93%) with undetectable HIV load. Among the 25 with paired pretreatment and posttreatment CD4 cell counts, the counts increased (mean [SD] change, 12.3 [28.5] /μL). Objective response rates were 30% for non-small cell lung cancer, 27% for melanoma, and 63% for Kaposi sarcoma.CONCLUSIONS AND RELEVANCE Immune checkpoint inhibitor therapy for the treatment of advanced-stage cancer in patients with HIV infection was associated with no new safety signals. Immune checkpoint inhibitors may be a safe and efficacious treatment option in this patient population. Several ongoing prospective clinical trials will shed further light on the safety and efficacy of ICI therapy in HIV-infected patients with cancer.

Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab

“…Pembrolizumab had a good safety profile and a sustained antitumoral response in this HIV-1-infected subject. Although the experience of pembrolizumab, as well as other ICIs, in people with HIV-1 is limited, these results are in line with other preliminary studies assessing the safety of ICI therapies in HIV-1-infected individuals with advanced-stage cancer [10,11]. However, only a fraction of these patients with advanced melanoma benefit from ICI blockade [10,11], which highlights this case of complete remission of this metastatic melanoma.…”

“…Although the experience of pembrolizumab, as well as other ICIs, in people with HIV-1 is limited, these results are in line with other preliminary studies assessing the safety of ICI therapies in HIV-1-infected individuals with advanced-stage cancer [10,11]. However, only a fraction of these patients with advanced melanoma benefit from ICI blockade [10,11], which highlights this case of complete remission of this metastatic melanoma. Immunologically, over the first nine weeks, we found an increase of HLA-DR + /CD38 + expressing cells, especially in T EM and T E CD8 + T-cell subsets, which had also been reported previously [18].…”

Management of immune checkpoint inhibitor‐related adverse events: A review of case reports

“…However, this case failed to explain the relationship between HIV infection and AEs. ICIs for the treatment of advanced‐stage cancer in patients with HIV infection might be associated with no new safety signals …”

“…ICIs for the treatment of advanced-stage cancer in patients with HIV infection might be associated with no new safety signals. 29…”

Treatment selection for first‐line metastatic renal cell carcinoma in Australia: Impact of new therapy options

“…Whether this applies to patients with a concurrent flare of their autoimmune disorder receiving active treatment with high doses of immunosuppression or steroids is unclear as these patients were typically not included in even the retrospective series. Recent data suggest that immunotherapy is well tolerated in patients with treated HIV, or concurrent hepatitis B and C . Given the risk of organ rejection with IO, patients with organ transplants should not receive IO treatment …”