Anti–PD-1 Therapy OK for Most with HIV

The PD-1 inhibitor pembrolizumab (Keytruda; Merck) poses no significant risks for patients with HIV and cancer, according to interim data from a phase I study presented during the Society for Immunotherapy of Cancer (SITC) conference held last month in National Harbor, MD. The findings suggest that patients with HIV should no longer be excluded from clinical trials testing checkpoint inhibitor therapies for various cancers.

In the ongoing study, investigators are evaluating the safety of pembrolizumab in three cohorts of patients infected with HIV based on CD4 T-cell count (100–199, 200–350, and >350). All patients had relapsed or refractory cancers and were taking HIV antiretroviral therapy (ART). In an interim analysis of 36 patients, HIV remained suppressed in all patients after a median of 12 weeks of treatment.

“As more effective and better-tolerated treatments have become available over the past 20 years, many HIV patients are aging and being diagnosed with a wider variety of cancers,” notes Thomas Uldrick, MD, senior clinician in the HIV and AIDS Malignancy Branch of the NCI's Center for Cancer Research in Bethesda, MD. In particular, they have an increased risk of developing HIV-related cancers—including B-cell lymphomas and Kaposi sarcoma—as well as non–HIV-related solid tumors.

“Cancer is now the leading cause of death in HIV patients,” says Uldrick. “As a result, we need to rethink the way we treat these patients and ensure that they are able to participate in clinical trials when appropriate.”

Due to concerns about the risk of infections and toxicities in patients with a compromised immune system, those with HIV have long been excluded from oncology trials. However, modern HIV treatments can restore immune function in most patients, with minimal adverse effects.

“HIV-positive patients now live as long as most uninfected people, so it no longer makes sense to continue excluding them from clinical trials when they get cancer,” says Edward Kim, MD, chair of Solid Tumor Oncology at Levine Cancer Institute, Carolinas Healthcare System, in Charlotte, NC. “To date, clinical trials have been so exclusionary that we have very little data on how checkpoint inhibitors work in HIV patients.”

The interim data supports recommendations made by an American Society of Clinical Oncology working group, led by Uldrick, stating that eligibility for trials should be based on CD4 T-cell counts, as well as any history of AIDS complications and effective treatment with ART.

Although most of those in the study fared well with pembrolizumab, additional research is needed in select patients, notes Uldrick. For example, one patient who had been previously diagnosed with Kaposi sarcoma (KS) and KS herpesvirus (KSHV)–inflammatory cytokine syndrome died after experiencing a sharp rise in KSHV viral load following pembrolizumab treatment, suggesting that those with KSHV-associated diseases or unexplained viruses require special consideration. In general, however, it's reasonable to prescribe treatment based on CD4 T-cell counts to gauge the risk of opportunistic infections, he says.

“It's become clear that we should not treat HIV patients [with cancer] differently from other cancer patients when it comes to clinical trials,” says Uldrick. “We now need to establish criteria to help us select patients who are healthy enough and would do well in the long run if not for their cancer.” –Janet Colwell