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Original Investigation
June 2, 2019

Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

Author Affiliations
  • 1Fred Hutchinson Cancer Research Center, Cancer Immunotherapy Trials Network, Seattle, Washington
  • 2HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 3Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York
  • 4Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, New York
  • 5Yale University, New Haven, Connecticut
  • 6Roswell Park Cancer Institute, Buffalo, New York
  • 7University of California San Francisco, San Francisco
  • 8Louisiana State University Health Science Center, New Orleans
  • 9Pardee Center for Infectious Diseases, University of North Carolina Health Care, Hendersonville
  • 10Axio Research, Seattle, Washington
  • 11Zuckerberg San Francisco General Hospital, San Francisco, California
JAMA Oncol. Published online June 2, 2019. doi:10.1001/jamaoncol.2019.2244
Key Points

Question  Is anti−PD-1 (anti−programmed cell death 1) therapy safe to administer in people with HIV with a range of CD4+ T-cell counts and cancer?

Findings  In this multicenter, open-label, nonrandomized, phase 1 study of 30 participants with HIV, a CD4 count of greater than 100 cells/μL, and advanced cancer, pembrolizumab had an acceptable safety profile, although an unexpected treatment-emergent adverse event of Kaposi sarcoma herpesvirus-associated polyclonal B-cell lymphoproliferation was noted. Clinical benefit was observed in participants with Kaposi sarcoma, primary effusion lymphoma, diffuse large B-cell lymphoma, and lung cancer.

Meaning  Anti−PD-1 therapy is appropriate for US Food and Drug Administration−approved indications and clinical trials in people with HIV.


Importance  Anti−PD-1 (anti−programmed cell death 1) and anti−PD-L1 (anti−programmed cell death ligand 1) regimens are preferred therapies for many cancers, including cancers associated with HIV. However, patients with HIV were excluded from most registered trials.

Objective  The primary objective was to evaluate the safety of pembrolizumab in people with HIV and advanced cancer; the secondary objective was to evaluate tumor responses.

Design, Setting, and Participants  Open-label, nonrandomized, phase 1 multicenter study conducted at 7 Cancer Immunotherapy Trials Network sites. Patients with HIV and advanced cancer as well as a CD4 count greater than or equal to 100 cells/μL, antiretroviral therapy (ART) for 4 or more weeks, and an HIV viral load of less than 200 copies/mL were eligible. Exclusion criteria included uncontrolled hepatitis B or C infection, active immunosuppressive therapy, or a history of autoimmune disease requiring systemic therapy.

Interventions  Pembrolizumab, 200 mg, administered intravenously every 3 weeks for up to 35 doses in 3 CD4 count−defined cohorts. Participants continued ART.

Main Outcomes and Measures  Safety and tolerability were assessed using current NCI Common Terminology Criteria for Adverse Events. Immune-related adverse events grade 2 or higher were considered immune-related events of clinical interest (irECI). Tumor responses were evaluated using standard tumor-specific criteria.

Results  Thirty participants (28 men and 2 women; median [range] age, 57 [39-77] years) were enrolled from April 2016 through March 2018; 6 had Kaposi sarcoma (KS), 5 had non-Hodgkin lymphoma (NHL), and 19 had non−AIDS-defining cancers. Safety was observed over 183 cycles of treatment with pembrolizumab. Most treatment-emergent adverse events at least possibly attributed to pembrolizumab were grade 1 or 2 (n = 22), and 20% (n = 6) were grade 3. The irECI included hypothyroidism (6 participants), pneumonitis (3 participants), rash (2 participants), an elevated aminotransferase/alanine aminotransferase level (1 participant), and a musculoskeletal event (1 participant). One participant with pretreatment KS herpesvirus (KSHV) viremia developed a polyclonal KSHV-associated B-cell lymphoproliferation and died. HIV was controlled in all participants. Increases in CD4 count were not statistically significant (median increase, 19 cells/μL; P = .18). Best tumor responses included complete response (lung, 1 patient), partial response (NHL, 2 patients), stable disease for 24 weeks or more (KS, 2 patients), stable disease for less than 24 weeks (15 patients), and progressive disease (8 patients); 2 patients were not evaluable.

Conclusions and Relevance  Pembrolizumab has acceptable safety in patients with cancer, HIV treated with ART, and a CD4+ T-cell count of greater than 100 cells/μL but may be associated with KSHV-associated B-cell lymphoproliferation. Clinical benefit was noted in lung cancer, NHL, and KS. Anti−PD-1 therapy is appropriate for US Food and Drug Administration−approved indications and clinical trials in this population.

Trial Registration  ClinicalTrials.gov identifier: NCT02595866