Checkpoint Blockade Demonstrates Antitumor Activity in HIV-Associated Kaposi Sarcoma

Although the incidence ratio of HIV-associated Kaposi sarcoma has fallen from 22,100 to 3634, primarily as a result of an increase in the administration of antiretroviral therapies (ART) in HIV, use of ART can also promote partial Kaposi sarcoma regression under certain conditions, and approximately 15% of HIV-infected individuals with a high CD4 count and high viral load still develop Kaposi sarcoma.¹

Virally associated tumors often overexpress PD-L1, which formed the basis of a hypothesis from a research team from the University of California, San Diego, which explored how checkpoint inhibition would work in Kaposi sarcoma. They analyzed records of 320 patients who were treated at the University’s Rebecca and John Moores Cancer Center in La Jolla from August 2013 to December 2017; of these patients, 9 were determined to have Kaposi sarcoma.

Next-generation sequencing was performed on samples from these 9 patients using the FoundationOne assay, which detects 405 genes. Information on blood levels of ctDNA was also obtained for some patients, and was measured by the Guardant panel — and in 4 of these 7 patients, no alterations in ctDNA were detected.

Most patients had received medication prior to study initiation, and all patients were receiving ART, with viral load in 7 of 9 patients considered well controlled before checkpoint inhibition.

Eight patients received nivolumab and 1 patient received pembrolizumab. The response rate was 66.6%, with 5 partial remissions (regressions in either the cutaneous or noncutaneous sites of disease) and 1 complete remission, in which the disease disappeared completely. At 33 years of age, the patient who achieved remission was the youngest participant among the 9 patients enrolled in the study.

And, the remaining 3 patients who did not see a remission experienced ongoing disease that was considered stable. None of the 9 patients exhibited disease progression during treatment with the checkpoint inhibitors, and no drug-related toxicities greater than grade 2 were observed.

In addition, 7 of the 9 patients (78%) saw an increase in CD4⁺ cell counts of a median of +104 cells/μl (P = .09). Overall, 6 of 9 patients (67%) were found to have an objective response. The researchers wrote that their finding support an earlier study that found major clinical responses in 2 patients with non-HIV-associated Kaposi sarcoma following treatment with nivolumab.²

The fact that PD-1 blockade antibodies have limited drug interactions makes them an appealing treatment option for those who are receiving ART, the researchers concluded. “Taken together, the side-effect profile of PD-1 antibodies, unlike that of cytotoxic chemotherapy, is not associated with further myelosuppression, making the use of these agents an attractive option for patients with HIV,” they wrote.

References

1. Galanina N, Goodman AM, Cohen PR, Frampton GM, and Kurzrock R. Successful treatment of HIV-associated Kaposi sarcoma with immune checkpoint blockade [published online September 7, 2018]. Cancer Immunol Res. doi: 10.1158/2326-6066.CIR-18-0121
2. Delyon J, Bizot A, Battistella M, Madelaine I, Vercellino L, Lebbé C. PD-1 blockade with nivolumab in endemic Kaposi sarcoma. Ann Oncol. 2018;29(4):1067-1069. doi: 10.1093/annonc/mdy006

This article originally appeared on Cancer Therapy Advisor