Widespread use of antiretroviral therapy in the treatment of patients infected with human immunodeficiency virus (HIV) has led to a decline in the incidence of HIV-related Kaposi sarcoma, an incurable malignancy associated with HIV. Nevertheless, about 15% of these patients will go on to develop Kaposi sarcoma.
A small study investigating the effectiveness of immune checkpoint inhibitors in patients with HIV-related Kaposi sarcoma has found that the therapy demonstrated significant antitumor activity and low toxicity, even in the presence of low tumor mutational burden. Longer follow-up and larger prospective trials with immune checkpoint inhibitors are needed to determine if an association between the Kaposi sarcoma mutanome and immune responsiveness exists. The study by Galanina et al is published in Cancer Immunology Research.
The study researchers analyzed the medical records of 320 patients treated with immune checkpoint inhibitors from 2013 to 2017 at the Moores Cancer Center at the University of California (UC), San Diego. Of these patients, 17 had HIV-associated malignancies, including 9 men with Kaposi sarcoma. All patients had received retroviral therapy and a median of one line of treatment for Kaposi sarcoma. Eight of the patients had received nivolumab (Opdivo) every 2 weeks, and one patient had received pembrolizumab (Keytruda) every 3 weeks.
In addition to survival data, the researchers utilized next-generation sequencing data from tissue and circulating tumor DNA (ctDNA) to analyze tumor mutational burden and programmed cell death ligand 1 (PD-L1) expression levels, biomarkers for anti–PD-L1 treatment.
Following treatment with immune checkpoint inhibition, 5 patients had a partial response, 3 had stable disease, and 1 patient had a complete remission. All patients remained on treatment, and no patient had shown disease progression at 6.5 months of follow-up.
In addition, the researchers found that 4 evaluable patients each showed anomalies in distinct genes, including TP53, KRAS, TLL2, PTPN6 (tissue and/or ctDNA), and NF1 (ctDNA). Tumor mutational burden was low, and PD-L1 immunohistochemistry was negative (3 and 4 assessable patients, respectively). Responders included patients with low CD4 counts, high HIV load, and/or visceral disease.
“Typically, checkpoint blockade immunotherapy is more effective in patients with high [tumor mutational burden] and/or high expression of PD-L1, yet we saw many patients who responded to treatment without these characteristics,” said Natalie Galanina, MD, an oncologist and Assistant Professor of Medicine at Moores Cancer Center at UC San Diego Health and lead author of the study. “It is possible that the viral immunogenomic mutanome is sufficient to induce changes to the immune system, enabling a response to treatment with checkpoint inhibition.”
Dr. Galanina is the corresponding author of this study.
Disclosure: Senior author Razelle Kurzrock, MD, reported receiving commercial research support from Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, and Konica Minolta; has received speakers bureau honoraria from Roche; has ownership interest in Curematch, Inc; and is a consultant/advisory board member for LOXO, X-Biotech, Actuate Therapeutics, Genentech, and NeoMed. No conflicts of interest were disclosed by the other study authors.
Funding for the study was provided by the National Cancer Institute and the Joan and Irwin Jacobs Fund.
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