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

Key PointsQuestionIs 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? FindingsIn this multicenter, open-label, nonrandomized, phase 1 study of 30 participants with HIV, a CD4 count of greater than 100 cells/mu L, 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. MeaningAnti-PD-1 therapy is appropriate for US Food and Drug Administration-approved indications and clinical trials in people with HIV. This open-label, nonrandomized, phase 1 study assesses the safety of pembrolizumab in patients with HIV and advanced cancer. ImportanceAnti-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. ObjectiveThe 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 ParticipantsOpen-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/mu L, 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. InterventionsPembrolizumab, 200 mg, administered intravenously every 3 weeks for up to 35 doses in 3 CD4 count-defined cohorts. Participants continued ART. Main Outcomes and MeasuresSafety 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. ResultsThirty 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/mu L; 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 RelevancePembrolizumab has acceptable safety in patients with cancer, HIV treated with ART, and a CD4(+) T-cell count of greater than 100 cells/mu L 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 RegistrationClinicalTrials.gov identifier: NCT02595866