Checkpoint inhibitor study suggests new treatment options for patients long excluded from cancer immunotherapy clinical trials.

A new category of immunotherapies called checkpoint inhibitors that has been highly effective against many different cancers appears safe to use in patients with both advanced malignancies and HIV, a population excluded from earlier trials of such therapies, according to an early-phase trial.

Principal investigator Dr. Thomas Uldrick of the HIV & AIDS Malignancy Branch at the National Cancer Institute will present late breaking results from the first 17 patients on a Phase 1 study of pembrolizumab in patients with HIV and advanced cancers at the Society for Immunotherapy of Cancer’s Annual Meeting. The ongoing, multi-site study is being conducted by the NCI-funded Cancer Immunotherapy Trials Network, which is headquartered at Fred Hutchinson Cancer Research Center.

Cancer has become the leading cause of death for people with HIV. But until now, they and their physicians have had little data to guide them on whether they can safely use powerful new anti-cancer drugs called immune checkpoint inhibitors.

“During the development of these drugs, people with HIV were routinely excluded from studies due to concerns that they would not tolerate these medications or perhaps not benefit from them because of their underlying HIV and associated immune dysfunction,” Uldrick said. “The most important first step was to show that this class of drug would be safe in certain cancer patients with HIV.”

Study participants—who were on standard antiretroviral therapy to control their HIV infections and had various cancers that had failed to respond to standard therapies—received pembrolizumab (Keytruda). Pembrolizumab belongs to a type of immunotherapy that blocks a braking system cancers use to tamp down the immune response. Checkpoint inhibitors have been extremely effective in some patients with advanced cancers otherwise thought untreatable. The treatments have received U.S. Food and Drug Administration approval for melanoma, lung cancer, head and neck cancer, Hodgkin’s lymphoma, and kidney and bladder cancers.

“These drugs are the backbone of cancer immunotherapy at present and have been shown to be effective in subsets of virtually every different kind of cancer,” said Fred Hutch immunotherapy researcher Dr. Martin Cheever, who leads the Cancer Immunotherapy Trials Network and is senior author of the new study. “For patients with HIV who are using effective antiretroviral therapy and have cancers for which these drugs are approved, there’s no reason not to consider these drugs as standard therapy.”

From the earliest days of the AIDS pandemic, a trio of cancers became known as AIDS-defining malignancies. A rare cancer called Kaposi sarcoma, non-Hodgkin lymphoma and, in women, cervical cancer often signaled that a person’s HIV infection had progressed to full-blown AIDS. People did not die of AIDS, per se. They died of one of these cancers or of infections like pneumocystis pneumonia and toxoplasmosis that took advantage of a weakened immune system.

Since the advent of antiretroviral therapy for HIV in 1996, full-blown AIDS and AIDS deaths have dropped dramatically. But the association between HIV and cancer remains, and not just with the traditional AIDS-defining malignancies. A large study published in the journal Annals of Internal Medicine in 2015 found higher cancer incidence across the board in HIV patients, including lung cancer and Hodgkin lymphoma.

The ongoing study will enroll up to 36 patients, and there are plans to include more patients with Kaposi sarcoma, a cancer for which checkpoint inhibitors have not been studied.

Although the NCI has recommended including people with HIV in immunotherapy clinical trials for a decade, virtually every industry-sponsored study over the last five years excluded them, according to a review by Uldrick a