In the Journals

Immune checkpoint inhibitors benefit patients with HIV, advanced cancer

Immune checkpoint inhibitor therapy appeared to be a safe, effective treatment for patients with advanced-stage cancer and HIV infection, according to a systematic review published in JAMA Oncology.

Cancer patients with HIV and their oncologists have found themselves in a real conundrum,” Chul Kim, MD, MPH, assistant professor at Georgetown Lombardi Comprehensive Cancer Center and attending physician at MedStar Georgetown University Hospital and MedStar Washington Hospital Center, said in a press release. “Because of their HIV infection, they are at higher risk [for] developing cancer than people who are not infected. In fact, cancer has become one of the leading causes of death in patients with HIV.

“But, conventional chemotherapies can reverse HIV suppression and, on top of that, these patients are widely excluded from clinical studies that test the next generation of cancer treatments,” Kim added.

Kim and colleagues searched PubMed for the keyword “HIV” and FDA-approved immune checkpoint inhibitors, including ipilimumab (Yervoy, Bristol-Myers Squibb), nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck), avelumab (Bavencio, EMD Serono), atezolizumab (Tecentriq, Genentech) and durvalumab (Imfinzi, AstraZeneca).

They identified 49 articles — of which they included 13, consisting of 11 case reports and two case series — and four meeting abstracts.

The studies involved 73 patients (90.4% men; mean age, 56.1 years; range, 30-77) with HIV who were being treated with immune checkpoint inhibitors for advanced-stage cancer. The most common cancer types included non-small cell lung cancer (34.2%), melanoma (21.9%) and Kaposi sarcoma (12.3%).

Of these patients, 62 received anti-PD-1 treatment, six received anti-CTLA-4 treatment, four received anti-PD-1 plus anti-CTLA-4 therapy, and one received sequential ipilimumab and nivolumab therapy. Ninety-five percent of patients received antiretroviral therapy at the time of immunotherapy treatment.

Overall, patients tolerated immune checkpoint inhibitor therapy well, with six of 70 patients (8.6%) experiencing grade 3 or higher immune-related adverse events, including insulin-dependent diabetes, colitis, myositis and hepatitis. Four of these patients received ipilimumab-containing regimens.

Thirty-four patients had documented HIV loads before and after treatment.

Five of six patients with detectable HIV load prior to treatment showed a decrease in viral load, four of whom had undetectable viral load after immune checkpoint inhibitor therapy.

Kim called this finding “intriguing.”

“It could be that immune checkpoint inhibitors are helping to suppress HIV, although this needs to be verified in future studies,” he said.

Two of 28 patients with undetectable HIV load at baseline had HIV become detectable in blood during treatment.

Fourteen of 25 patients (56%) with documented CD4 cell counts before and after treatment showed an increase in CD4 count, whereas 11 patients (44%) had a decrease in CD4 cell count after initiation of immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors induced objective response rates of 30% among patients with NSCLC, 27% among patients with melanoma, and 63% among patients with Kaposi sarcoma.

Georgetown Lombardi Comprehensive Cancer Center plans to launch a clinical trial assessing checkpoint inhibitor therapy as first-line treatment for patients with lung cancer and HIV or viral hepatitis.

“We will be able to look at what effects checkpoint inhibitor therapy has on both the cancer and the infection,” Kim said.

According to Kim, the promising results in this and other studies warrant continued research.

“There are signals in this analysis and other studies that suggest these new cancer drugs may restore an immune response against HIV in patients whose immune system is exhausted by a long fight with HIV.” – by Jennifer Byrne

Disclosures: Kim reports personal fees from CARIS Life Science outside the submitted work, and research support and funding to his institution from AstraZeneca. The other author reports no relevant financial disclosures.

Immune checkpoint inhibitor therapy appeared to be a safe, effective treatment for patients with advanced-stage cancer and HIV infection, according to a systematic review published in JAMA Oncology.

Cancer patients with HIV and their oncologists have found themselves in a real conundrum,” Chul Kim, MD, MPH, assistant professor at Georgetown Lombardi Comprehensive Cancer Center and attending physician at MedStar Georgetown University Hospital and MedStar Washington Hospital Center, said in a press release. “Because of their HIV infection, they are at higher risk [for] developing cancer than people who are not infected. In fact, cancer has become one of the leading causes of death in patients with HIV.

“But, conventional chemotherapies can reverse HIV suppression and, on top of that, these patients are widely excluded from clinical studies that test the next generation of cancer treatments,” Kim added.

Kim and colleagues searched PubMed for the keyword “HIV” and FDA-approved immune checkpoint inhibitors, including ipilimumab (Yervoy, Bristol-Myers Squibb), nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck), avelumab (Bavencio, EMD Serono), atezolizumab (Tecentriq, Genentech) and durvalumab (Imfinzi, AstraZeneca).

They identified 49 articles — of which they included 13, consisting of 11 case reports and two case series — and four meeting abstracts.

The studies involved 73 patients (90.4% men; mean age, 56.1 years; range, 30-77) with HIV who were being treated with immune checkpoint inhibitors for advanced-stage cancer. The most common cancer types included non-small cell lung cancer (34.2%), melanoma (21.9%) and Kaposi sarcoma (12.3%).

Of these patients, 62 received anti-PD-1 treatment, six received anti-CTLA-4 treatment, four received anti-PD-1 plus anti-CTLA-4 therapy, and one received sequential ipilimumab and nivolumab therapy. Ninety-five percent of patients received antiretroviral therapy at the time of immunotherapy treatment.

Overall, patients tolerated immune checkpoint inhibitor therapy well, with six of 70 patients (8.6%) experiencing grade 3 or higher immune-related adverse events, including insulin-dependent diabetes, colitis, myositis and hepatitis. Four of these patients received ipilimumab-containing regimens.

Thirty-four patients had documented HIV loads before and after treatment.

Five of six patients with detectable HIV load prior to treatment showed a decrease in viral load, four of whom had undetectable viral load after immune checkpoint inhibitor therapy.

Kim called this finding “intriguing.”

“It could be that immune checkpoint inhibitors are helping to suppress HIV, although this needs to be verified in future studies,” he said.

Two of 28 patients with undetectable HIV load at baseline had HIV become detectable in blood during treatment.

Fourteen of 25 patients (56%) with documented CD4 cell counts before and after treatment showed an increase in CD4 count, whereas 11 patients (44%) had a decrease in CD4 cell count after initiation of immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors induced objective response rates of 30% among patients with NSCLC, 27% among patients with melanoma, and 63% among patients with Kaposi sarcoma.

Georgetown Lombardi Comprehensive Cancer Center plans to launch a clinical trial assessing checkpoint inhibitor therapy as first-line treatment for patients with lung cancer and HIV or viral hepatitis.

“We will be able to look at what effects checkpoint inhibitor therapy has on both the cancer and the infection,” Kim said.

According to Kim, the promising results in this and other studies warrant continued research.

“There are signals in this analysis and other studies that suggest these new cancer drugs may restore an immune response against HIV in patients whose immune system is exhausted by a long fight with HIV.” – by Jennifer Byrne

Disclosures: Kim reports personal fees from CARIS Life Science outside the submitted work, and research support and funding to his institution from AstraZeneca. The other author reports no relevant financial disclosures.

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