IMPORTANCEPatients 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.
AbstractsBackgroundPatients with chronic viral infections including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) are at increased risk of developing malignancies. The safety and efficacy of ICI therapy in patients with both cancer and chronic viral infections is not well established as most clinical trials of ICIs excluded these patient populations.MethodsWe performed a retrospective analysis of patients with advanced-stage cancers and HIV, HBV, or HCV infection treated with ICI therapy at 5 MedStar Health hospitals from January 2011 to April 2018.ResultsWe identified 50 patients including 16 HIV, 29 HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. In the HIV cohort (n = 21), any grade immune-related adverse events (irAEs) were 24% with grade ≥ 3 irAEs 14%. Among 5 patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cell counts were observed. RECIST confirmed (n = 18) overall response rate (ORR) was 28% with 2 complete responses (CR) and 3 partial responses (PR). Responders included 2 patients with low baseline CD4+ T-cell counts (40 and 77 cells/ul, respectively). In the HBV/HCV cohort (n = 34), any grade irAEs were 44% with grade ≥ 3 irAEs 29%. RECIST confirmed ORR was 21% (6 PR). Among the 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), there was no evidence of viral reactivation.ConclusionsOur retrospective series is one of the largest case series to report clinical outcomes among HIV, HBV and HCV patients treated with ICI therapy. Toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. Viral reactivation was not observed. Tumor responses occurred in HIV patients with low CD4 T-cell counts. While prospective studies are needed to validate above findings, these data support not excluding such patients from ICI–based clinical trials or treatment.
Relapsed/refractory primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 CAR T-cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We therefore performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (ICANS and CRS) as well as response rates in these two populations. 70% of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the PCNSL patients, 56% achieved a CR with 37% remaining in remission at 6 months. Similarly, 47% of SCNSL patients had a CR, with 37% in remission at 6 months. In a large meta-analysis of CNS lymphomas, toxicity of anti-CD19 CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL
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