Phase 1 Study Demonstrates Safety of Pembrolizumab in Patients With HIV and Advanced Cancer

A phase 1 study assessing pembrolizumab in patients living with HIV and advanced cancer yielded positive results, with researchers concluding that the anti—programmed cell death ligand 1 (PD-L1) inhibitor is appropriate for current FDA-approved indications and clinical trials for this patient population.

The study findings could have important implications for clinical trial participation for people living with HIV, who have historically been excluded from trials and who have an increased risk of developing a range of cancers, such as Kaposi sarcoma (KS), lung cancer, and head and neck squamous cell carcinoma.

“Exclusion of people with HIV in clinical trials is a longstanding problem that grew out of the poor outcomes of AIDS patients with cancer, before there were effective antiviral therapies for HIV,” said Tom Uldrick Jr, MD, MS, associate professor of Medicine at the University of Washington School of Medicine, researcher at Fred Hutchinson Cancer Research Center, and lead author of the study, in a statement. Because of this, there’s a gap in knowledge regarding if and how these patients would respond to treatments.

In the current study, published in JAMA Oncology, researchers examined the impact of the PD-L1 inhibitor among 30 patients with cancer and well-controlled HIV while on antiretroviral therapy (ART). Patients were enrolled in the study between April 2016 and March 2018 from 7 Cancer Immunotherapy Trials Network sites.

With patients receiving pembrolizumab 200 mg every 3 weeks for up to 35 doses, researchers were able to observe more than 183 cycles of treatment and found that the majority (73%) of treatment-related adverse events were grade 1 or grade 2. Meanwhile, 6 (20%) of the adverse events were grade 3. The most common adverse events, which occurred in at least 20% of patients, included anemia, fatigue, nausea, and hypothyroidism. According to the researchers, most serious adverse events were attributed to complications of advanced cancer.

“The current study has demonstrated that pembrolizumab has a similar adverse event profile for people with HIV and advanced cancer who have suppressed HIV on ART to that observed in published studies of participants without HIV,” they wrote.

Immune-related events of clinical interest included hypothyroidism (2 patients), pneumonitis (3 patients), rash (2 patients), an elevated musculoskeletal/alanine aminotransferase level (1 patient), and a musculoskeletal event (1 patient).

The researchers noted that there was 1 patient with pretreated KS herpesvirus (KSHV) viremia who developed a polyclonal KSHV-associated B-cell lymphoproliferation and died.

The best responses to the treatment were observed among 1 patient with lung cancer who achieved a complete response, 2 patients with non-Hodgkin lymphoma who achieved a partial response, and 2 patients with Kaposi sarcoma who achieved stable disease for at least 24 weeks. There were 15 patients who achieved stable disease for less than 24 weeks, 8 patients who had progressive disease, and 2 patients who were unable to be evaluated.

“The current study demonstrates that pembrolizumab monotherapy does not appear to have a detrimental effect on CD4+ T-cell counts,” added the researchers. “In the setting of relapsed and refractory cancers, CD4+ T-cell counts tended to increase during the study, although the increases were not statistically significant.”

Throughout the study period, 23 (77%) patients remained virally suppressed, and low-level viremia of no significance (blips less than 100 copies/mL) was observed in 7 patients.

Reference

Uldrick T, Goncalves P, Abdul-Hay, et al. Assessment of the safety of pembrolizumab in patients with HIV and advanced cancer—a phase 1 study [published online June 2, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.2244.