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

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.