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

Educational Objective
To learn the safety and efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and advanced cancer.
1 Credit CME
Key Points

Question  Is immune checkpoint inhibitor therapy safe and efficacious in patients with HIV infection and advanced-stage cancer?

Findings  This systematic review of 13 articles plus 4 meeting presentations found that immune checkpoint inhibitor therapy was well tolerated, with grade 3 or higher immune-related adverse events identified in 6 of 70 patients, and had no association with adverse changes in HIV load or CD4 cell count. Antitumor activity was observed in various cancer types including non–small cell lung cancer, melanoma, and Kaposi sarcoma.

Meaning  Immune checkpoint inhibitor therapy appears to be safe and efficacious in HIV-infected individuals with advanced-stage cancer, although ongoing prospective trials of immune checkpoint inhibitors in this patient population will need to confirm these findings.

Abstract

Importance  Patients 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.

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Article Information

Accepted for Publication: October 18, 2018.

Corresponding Author: Chul Kim, MD, MPH, Department of Medicine, Georgetown University, 3800 Reservoir Rd, NW, Pod B P417, Washington, DC 20057 (chul.kim@gunet.georgetown.edu).

Published Online: February 7, 2019. doi:10.1001/jamaoncol.2018.6737

Author Contributions: Drs Cook and Kim had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kim.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Both authors.

Critical revision of the manuscript for important intellectual content: Kim.

Statistical analysis: Kim.

Obtained funding: Kim.

Administrative, technical, or material support: Kim.

Supervision: Kim.

Conflict of Interest Disclosures: Dr Kim reported receiving personal fees from CARIS Life Science outside the submitted work, and receiving funding and other support for research to his institution from AstraZeneca. No other disclosures were reported.

Funding/Support: This study was supported by a Norman Rales Young Investigator Award from the American Society of Clinical Oncology Conquer Cancer Foundation and a Sher research grant from Georgetown University (Dr Kim).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Mark M. Awad, MD, PhD, of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, and Amélie Guihot-Thévenin, MD, PhD, of the Département d’Immunologie, AP-HP, Hôpital Pitié Salpêtrière, provided further information on their patients. Neither was compensated for their work.

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