The results are likely applicable to other immune checkpoint inhibitors targeting the same pathway as Keytruda, the investigators said.
The findings were recently presented in an oral presentation, titled “Phase I study of pembrolizumab in people with HIV and cancer,” at the 2019 American Society of Clinical Oncology Annual Meeting. They were simultaneously published in JAMA Oncology.
Despite treatment advances, HIV-positive patients still have an increased risk of developing a wide variety of cancers, including B-cell non-Hodgkin’s lymphoma (NHL), Kaposi sarcoma (KS), lung cancer, squamous cell skin cancer, head and neck squamous cell carcinoma, classic Hodgkin’s lymphoma, and hepatocellular carcinoma).
“Immunotherapy may be beneficial for treating HIV-associated cancers; however, people living with HIV have been often excluded from cancer clinical trials that test novel agents,” the researchers wrote.
Keytruda is a checkpoint blockade immunotherapy developed by Merck (known as MSD outside the U.S. and Canada) which has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of several types of cancer.
It is a monoclonal antibody that has been designed to target and block the activity of the PD-1 receptor (a protein found on the surface of immune cells), preventing cancer cells from avoiding being targeted and killed by immune cells.
“Prospective anti-PD-1 safety data are required to guide the treatment of patients with HIV and cancer with what is now standard-of-care immunotherapy and to inform HIV-related eligibility criteria for future immuno-oncology studies. We hypothesized that anti-PD-1 therapy would be safe and active in people with cancer and HIV that is well controlled on ART [antiretroviral therapy],” the investigators wrote.
To test their hypothesis, the researchers carried out a multicenter, open-label, Phase 1 trial (NCT02595866) in which HIV-positive patients, who had received at least four weeks of ART and had been diagnosed with different types of cancers, were treated with Keytruda administered at a dose of 200 mg intravenously, every three weeks, for up to 35 doses.
The trial, sponsored by the National Cancer Institute, enrolled a total of 30 HIV-positive patients between April 2016 and March 2018.
From the 30 patients participating in the study, 11 (37%) had been diagnosed with AIDS-defining cancers, including KS and NHL, while 19 (63%) had been diagnosed with non-AIDS-defining cancers, including anal cancer and squamous cell skin cancer.
Treatment safety was assessed in all patients during 183 cycles of therapy with Keytruda. Most treatment-emergent adverse events (TEAEs) associated with Keytruda were either mild or moderate, and 20% were severe.
Immune-related events of clinical interest (irECI) — immune-related adverse events considered moderate or higher — included hypothyroidism (low thyroid function), pneumonitis (lung infection), rash, and high levels of aminotransferase and alanine aminotransferase (liver enzymes that, when elevated, may indicate liver inflammation or damage).
One of the patients died from a rare complication of KS herpes virus (KSHV)-associated B-cell lymphoproliferation. Despite not being directly linked to the use of Keytruda, based on this death, physicians recommend caution when using anti-PD-1 therapy in patients with KSHV-associated disorders.
Over the course of the trial, HIV was kept under control in all study participants, who remained on ART while receiving Keytruda.
In addition, the researchers found that treatment with Keytruda led to promising anti-cancer responses in some patients, including:
- A complete response (complete tumor eradication) in a patient with lung cancer.
- A partial response (significant decrease in tumor size, with no signs of cancer spreading) in two patients with NHL.
- Disease stabilization for more than 24 weeks in two KS patients.
- Disease stabilization for less than 24 weeks in 15 patients.
“Our conclusion is that anti-PD-1 therapy is appropriate for cancer patients with well-controlled HIV, and that patients with HIV and cancer can be treated with the drug and should be included in future immunotherapy studies,” Tom Uldrick, MD, a researcher at the Fred Hutchinson Cancer Research Center and lead author of the study, said in a press release.
The FDA, Friends of Cancer Research, and the American Society of Clinical Oncology have agreed that HIV-positive patients whose disease is kept under control should be allowed to participate in clinical trials assessing the effectiveness of anti-cancer therapies.