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Immunotherapy shows promise for HIV-associated Kaposi’s sarcoma
Anti-PD-1 immune checkpoint inhibitors demonstrated high efficacy with low toxicity in a small cohort of patients with HIV-positive Kaposi’s sarcoma, according to a study published in Cancer Immunology Research.
More than 65% of patients achieved partial or complete remission with immune checkpoint inhibition.
“Despite the successful and prevalent use of antiretroviral medications to treat HIV-positive patients, about 15% of this population still develops Kaposi’s sarcoma, which is an incurable malignancy with significant morbidity,” Natalie Galanina, MD, assistant professor of medicine at UC San Diego Health, said in a press release. “Due to a paucity of novel therapeutic options for this disease in recent decades, we wanted to investigate if immune checkpoint inhibition was effective in treating this virally mediated cancer.”
The researchers pooled data on nine men (median age, 44 years; range, 33-63) with HIV-positive Kaposi’s sarcoma treated with anti-PD-1 immune checkpoint inhibitors at Moores Cancer Center in San Diego between August 2013 and December 2017.
All patients received antiretroviral therapy and a median of one prior line of treatment for Kaposi’s sarcoma.
Eight patients received nivolumab (Opdivo, Bristol-Myers Squibb) and one received pembrolizumab (Keytruda, Merck).
In addition to monitoring patients for safety and efficacy, the researchers used next-generation sequencing data from tissue and circulating tumor DNA to analyze tumor mutational burden and PD-L1 expression levels.
Immune checkpoint inhibition induced a partial response in five patients, stable disease in three patients and complete remission in one patient, for a response rate of 66.6%. At 6.5 months follow-up, no patient had experienced disease progression and all patients remained on treatment.
Biological and molecular analyses showed PD-L1 expression was negative in four evaluable patients, and three evaluable patients had low tumor mutational burden.
“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,” Galanina said in the release. “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.”
Galanina also noted that treatment with PD-1 immune checkpoint inhibitors did not cause myelosuppression. Seven patients had an increase in both CD4-positive and CD8-positive T-cell levels, which was not statistically significant.
Still, the study may be limited by a small sample size and lack of available archival tissue material to validate PD-L1 expression findings, according to the researchers. – by Jennifer Southall
Disclosures: The study was funded in part by the NCI and the Joan and Irwin Jacobs Fund. Galanina reports no relevant financial disclosures. Please see the study for a list of all other authors’ relevant financial disclosures.