Largest Study of Black Patients With Cancer Aims to Show Better Responses to Immunotherapy

The first large study of Black patients receiving immune checkpoint inhibitors is underway to uncover differences in response to immunotherapy in Black patients compared with White patients, announced Roswell Park Comprehensive Cancer Center (Roswell Park), in a press release.¹

Assessment of this patient population was influenced by insights into the immune responses observed in Black patients who were treated at Roswell Park. The study is a collaborative effort between Roswell Park and the University of Rochester’s Wilmot Cancer Institute, and it is funded by a 2-year, $2.08 million grant from the National Cancer Institute (NCI).

“Checkpoint inhibitors have largely not been studied in Black cancer patients, but our recent findings show that there may be a particular benefit to these immunotherapies for cancer patients of African ancestry — across a variety of cancer types,” stated Christine Ambrosone, PhD, chair of Cancer Prevention & Control at Roswell Park and a co-investigator on the study.

In early 2021, a Roswell Park study led by Ambrosone and Song Yao, PhD, was published in the Journal of the National Cancer Institute. A distinct molecular signature in the tumor tissues of 1315 Black patients with breast cancer was discovered in the study, which was indicative of more aggressive disease that would benefit from treatment with immune checkpoint inhibitors. The signature found was a CD8+ T-cell signature, which also led to poorer survival outcomes in Black patients, especially if they had hormone receptor–positive breast cancer. Ambrosone et al noted in a press release around the published study that further investigation is based on the hypothesis that Black patients may have higher responses to immune checkpoint inhibition.^2,3

“Because Black cancer patients tend to have a prevalence of what we call ‘exhausted,’ nonfunctional T cells, we realized they may be more likely to do well on immune checkpoint inhibitors, which target the exhausted T cells to revive them and restore their ability to fight cancer cells,” Yao, professor of oncology in Roswell Park’s Department of Cancer Prevention and Control, co-principal investigator on the study, in the press release.1 “But we can’t know this without further study, and this new project will tackle that knowledge gap in a large and diverse patient population.”

Studies evaluating immunotherapies like nivolumab (Opdivo), and pembrolizumab (Keytruda) allowed these agents to become the standard of care for the treatment of 16 different malignancies in both the early and advanced settings. However, many of these studies had a low enrollment of individuals with African ancestry, leaving questions about how Black patients perform on immune checkpoint inhibitors.

At the Wilmot Cancer Institute, the leading investigators will include Charles Kamen, PhD, MPH, and Gary Morrow, PhD, MS.

To investigate these immune responses in Black patients, the study will enroll 600 Black patients and 1200 White patients of European ancestry. During the study, genetic analyses will be conducted to confirm African ancestry in each Black patient enrolled. In addition, the investigators will look into social determinants of health and other factors to predict immune response. Finally, the frequency of treatment delays due to severe adverse events in Black patients compared with White patients will be assessed along with short-term and long-term treatment outcomes.

"Our project is designed to get the full 360 picture of Black patients who receive immunotherapy," said Kamen, in a statement. "Not only are we measuring their response to treatment, but we're also looking at factors like discrimination by providers and health care systems and how often treatment is stopped so that we have a better understand of equity and access to high-quality care."

_References:

_{1. Roswell Park, Wilmot Cancer Institute collaborate on first large study of immunotherapy in black cancer patients. News release. April 20, 2021. Accessed April 21, 2021. https://bit.ly/3n4GZg4}

_{2. Aggressive breast cancers in black patients related to immune factors, Roswell Park team reveals. News release. January 5, 2021. Accessed April 21, 2021. https://bit.ly/32BLFQY}

_{3. Yao S, Cheng T, Elkhanany A, et al. Breast tumor microenvironment in black women: a distinct signature of CD8+ T-cell exhaustion. Journal of the National Cancer Institute.2021. doi: 10.1093/jnci/djaa215}