Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study
Mené sur 30 patients infectés par le VIH, recevant une thérapie antirétrovirale et atteints d'un cancer de stade avancé (âge médian : 57 ans), cet essai non randomisé de phase I évalue la toxicité et l'efficacité, du point de vue de la réponse tumorale, du pembrolizumab
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
JAMA Oncology 2019