- Pembrolizumab an immunotherapy appears safe for cancer patients with HIV.
- Immunotherapies called checkpoint inhibitors are highly effective against different cancers.
- The National Cancer Institute (NCI) recommends patients with HIV and malignancy be considered for immunotherapy.
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.
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.
‘Checkpoint inhibitors, a new category of immunotherapies are highly effective against many different cancers and appear safe to use in patients with both advanced malignancies and HIV.’
"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 "Mac" 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."
HIV and cancer
From the earliest days of the AIDS pandemic, Kaposi sarcoma -- a rarely seen cancer until then -- was one of a trio of cancers known as AIDS-defining malignancies. It, 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.
"Globally, more than 35 million people are infected with HIV, and cancer is the number one reason they are dying," Study Principal Investigator, Dr. Thomas Uldrick said. "Establishing proven effective regimens to manage cancer in people with HIV is critically important."
Further study in Kaposi sarcoma
Kaposi sarcoma is caused by the Kaposi sarcoma herpes virus (also known as human herpesvirus 8, or HHV-8) and most commonly appears as lesions on the skin. KSHV can also cause two other B-cell tumors, primary effusion lymphoma and a form of multicentric Castleman disease. Additionally, it can infect blood cells and spread through the bloodstream to infect other cells in the body, Uldrick said.
"We do not believe that this takes away from the safety message in patients with HIV and other, better studied cancers," Uldrick said. "However, more experience is clearly needed in treating KSHV-associated diseases with checkpoint inhibitors."
A passion to 'change the culture'
Although the National Cancer Institute 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 and others published in the Journal of Clinical Oncology. Uldrick believes that reluctance to include people with HIV in cancer immunotherapy studies dates back to a time when patients were still dying of opportunistic infections and antiretroviral therapies were more toxic than they are today.
Getting out the message
The ongoing study is now being conducted at eight sites, each of which includes physician-researchers with expertise in both cancer and HIV. A majority of the early patients were enrolled on the trial through Uldrick's group at the NCI Intramural Research Program in Bethesda, Maryland.
Uldrick will continue to lead the study after he leaves the NCI to become deputy head of Fred Hutch Global Oncology on Dec. 1.
He and Cheever are hoping that these early results lead to additional studies of checkpoint inhibitors in people with HIV and malignancies, especially those cancers that are more prevalent in people with HIV such as Kaposi sarcoma and cancers caused by another virus, human papillomavirus, such as cervical cancer.
In the meantime, the researchers intend to talk about their findings at multiple scientific communities so that people with HIV and their physicians become aware of the data.
"We'd recommend that patients with HIV and malignancy be considered for this therapy if it's approved for their particular cancer," Uldrick said.
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