Offering long-awaited insight to an unanswered question, researchers have found that treatment with immune checkpoint inhibitors for patients living with HIV and advanced-stage cancer is both safe and effective.
The answer has important implications, as people living with HIV are at an increased risk
of both first and secondary cancers as a result of living longer thanks to treatment advances like antiretroviral therapy, as well as having compromised immune systems. The patient population has historically been excluded from clinical trials, which has presented a research gap in knowing how, and if, these patients would respond to immunotherapy.
“Because checkpoint inhibitors manipulate the immune system, the concern has been that these therapies might have adverse effects such as virus reactivation with HIV infection,” noted a press release
from Georgetown Lombardi Comprehensive Cancer Center, where the researchers are from.
The researchers conducted a systematic review of immune checkpoint inhibitor therapy in these patients, identifying 13 articles and 4 meeting presentations published before April 16, 2018.
Among these studies, there were 73 cases of patients with HIV and advanced-stage cancer who received treatment with immune checkpoint inhibitors. The most common type of cancer was non–small cell lung cancer (NSCLC) (34.2%), followed by melanoma (21.9%) and Kaposi sarcoma (12.3%). The majority of patients (84.9%) were treated with anti–programmed cell death 1 (anti–PD-1) inhibitors, such as nivolumab and pembrolizumab. Other treatment regimens included anti–cytotoxic T-lymphocyte antigen 4 (anti–CTLA-4) inhibitors, a combination of the 2, or sequential treatment of ipilimumab and nivolumab.
Looking at the data, the researchers found that the immune checkpoint inhibitors provided patients with comparable objective response rates in NSCLC (30%) and melanoma (27%) that have been observed in non-infected patients with cancer. The treatments also showed significant response rates for Kaposi’s sarcoma (67%), a cancer that is strongly associated with HIV.
Following treatment, viral suppression remained for 26 of the 28 (93%) patients virally suppressed at baseline.
“In 6 patients who had a detectable load of HIV in the blood before treatment, 5 had a decrease in their viral load after treatment,” explained Chul Kim, MD, MPH, assistant professor at Georgetown Lombardi and an attending physician at MedStar Georgetown University Hospital and MedStar Washington Hospital Center, in a statement. “It could be that checkpoint inhibitors are helping to suppress HIV, although this finding needs to be verified in future studies.”
Reflecting on the safety data, the researchers said that there were no concerning findings with regard to immune-related toxic effects and changes in viral status or CD4 cell count. Similar to observations in patients without HIV, grade 3 or higher immune-related adverse events happened more frequently in patients treated with a combination of anti–PD-1 and anti–CTLA-4 inhibitors (nivolumab and ipilimumab).
Cook M, Kim C. Safety and efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and advanced-stage cancer [published online February 7, 2019]. JAMA Oncol
. doi: 10.1001/jamaoncol.2018.6737.