Beta-Blockers May Enhance Immunotherapy for Melanoma

Nick Mulcahy

January 12, 2018

Use of a specific type of β-blocker may enhance the effectiveness of immunotherapy in the treatment of metastatic melanoma, according to a retrospective chart review.

Researchers at Penn State University in College Park, Pennsylvania, report that patients with metastatic melanoma who received immunotherapy at their cancer center while taking a pan-β-blocker, such as propranolol, lived longer than patients who received immunotherapy alone or other types of β-blockers.

Specifically, among 195 patients with metastatic melanoma who were treated with immunotherapy (interleukin-2, cytotoxic t-lymphocyte associated protein 4, and/or programmed cell death-1 agents) between 2000 and 2015, the 5-year overall survival rate was about 70% for the group receiving pan-β-blockers (n = 17) vs about 25% for the groups taking β1-selective blockers (n = 45) or no β-blockers at all (n = 133).

The new study was published online December 21, 2017, as a brief report in OncoImmunology. " β-Blockers slow your heart rhythm, but they can also affect immune cells and improve immune function," commented senior study author, Todd Schell, PhD, professor of microbiology and immunology, in a press statement.

These drugs, which are inexpensive, are perhaps best known for their use in preventing heart attacks and lowering blood pressure.

Penn State is acting quickly on their results.

"In collaboration with colleagues at Roswell Park, we are in the midst of initiating a prospective clinical trial of concurrent propranolol and pembrolizumab for first-line treatment of patients with metastatic melanoma," said study author, Joseph Drabick, MD, professor of medicine, in an email to Medscape Medical News.

Dr Drabick said that he is now steering patients with melanoma already receiving β-blockers to propranolol.

"I have had some patients who were already on a non-pan-β-blocker for some reason (usually [atrial fibrillation] or hypertension) switch to propranolol while undergoing immunotherapy for metastatic melanoma…rather than stay on their non-pan-β-blocker," he explained.

The Penn State researchers also performed a follow-up experiment with mice and saw results similar to those of their retrospective chart review.

Additionally, the study authors point out that multiple observational studies have shown a positive correlation between β-blocker use and outcomes in breast and ovarian cancers.

The authors also say that preclinical studies have shown that under conditions of reduced physiologic stress, the T cell–dependent antitumor immune response is greatly enhanced and the efficacy of cancer therapies is improved. Other research indicates that β-adrenergic receptor (BAR)–driven stress suppresses immune response to malignancies.

Collectively, research to date suggests that "targeting the BAR signaling pathway directly to reduce stress signaling may provide an innovative approach to improve cancer treatment," the team writes.

The study was supported by the Pennsylvania Department of Health. Lead author, Kathleen Kokolus, MD, was supported by a National Cancer Institute training grant. The authors have disclosed no relevant financial relationships.

Oncoimmunology. Published online December 21, 2017. Abstract

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