Immunotherapy Shows Promise in Treating HIV-Associated Cancer

More than 65% of patients with Kaposi’s sarcoma in a small cohort had partial or complete remission when treated with immune checkpoint inhibitors.

With the availability of antiretroviral medications, outcomes for individuals with HIV have improved. However, approximately 15% of individuals with the virus still develop Kaposi’s sarcoma, an incurable HIV-associated malignancy that limits therapeutic options.

A new study, published in Cancer Immunology Research, found that treatment with immune checkpoint inhibitors may be effective in treating HIV-associated Kaposi’s sarcoma.

Currently, the standard of care for the cancer is liposomal doxorubicin, a type of chemotherapy. However, only half of patients respond to this therapy, and even so, treatment is not curative and the disease can persist in patients with an undetectable viral load.

For the study, the researchers analyzed data from 9 men with Kaposi’s sarcoma treated with anti-PD-1 immune checkpoint inhibitors at Moores Cancer Center between August 2013 and December 2017. Median viral load was 20 copies/mL and median CD4 count was 256 cells/μL.

All patients had received retroviral therapy and a median of 1 prior line of treatment. Eight patients were treated with nivolumab (Opdivo) and 1 patient was treated with pembrolizumab (Keytruda).

The researchers measured survival data and utilized next-generation sequencing data from tissue and circulating tumor DNA to analyze tumor mutational burden (TMB) and PD-L1 expression levels, which are biomarkers for anti-PD-L1 treatment.

Overall, 5 patients demonstrated a partial response to immune checkpoint inhibition, 3 patients had stable disease, and 1 patient had complete remission. All patients remained on treatment and no patients showed disease progression at 6.5 months of follow-up, according to the results.

Additionally, the researchers noted that PD-L1 expression was negative in all 4 evaluable patients and all 3 evaluable patients had low TMB.

“Typically, checkpoint blockade immunotherapy is more effective in patients with high TMB and/or high expression of PD-L1, yet we saw many patients who responded to treatment without these characteristics,” study author Natalie Galanina, MD, oncologist at Moores Cancer Center at UC San Diego Health, said in a press 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.”

Seven patients treated with PD-1 inhibitors had an increase in both CD4+ and CD8+ T cell levels, although it was not statistically significant. Responders included patients with low CD4 counts, high HIV load, and/or visceral disease.

“Based on these results, we think that PD-1 checkpoint blockade may present a promising, novel therapeutic option for HIV-associated Kaposi’s sarcoma with high efficacy and low toxicity,” Dr Galanina concluded.

References

Galanina N, Goodman AM, Cohen PR, et al. Successful treatment of HIV-associated Kaposi sarcoma with immune checkpoint blockade. Cancer Immunology Research. 2018. Doi: 10.1158/2326-6066.CIR-18-0121

Immunotherapy May Be Efficacious in Patients with HIV-Associated Kaposi’s Sarcoma [news release]. American Association for Cancer Research’s website. https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1217. Accessed September 7, 2018.