Some Allergy Medications May Positively Influence Immunotherapy Responses in Cancer, But Is Only ‘A Tip of the Iceberg’

Antihistamines, drugs commonly used to treat allergies, may improve responses in patients with cancer treated with immune checkpoint inhibitors, recent study findings demonstrated.

In particular, antihistamines reduce or block histamine, a chemical that white blood cells release into the bloodstream when as the immune system defends itself against a potential allergen.

“Our current findings suggest that cancer patients with allergy symptoms or high histamine levels could benefit from taking H1-antihistamines while receiving immunotherapy, but this must be confirmed first in prospective studies,” Dr. Dihua Yu, professor and chair ad interim of the Department of Molecular and Cellular Oncology and Hubert L. & Olive Stringer Distinguished Chair in Basic Science at The University of Texas MD Anderson Cancer Center in Houston, told CURE®.

Findings from this study also fills a knowledge gap in this area, Yu mentioned.

“Our study fills in this knowledge gap and provides mechanistic insight into the link between histamine and cancer,” she said. “We found that cancer cell-derived or allergic reaction-released histamine enables cancer cells to evade immune attack and resist immunotherapy.”

With this study, which was published in Cancer Cell,Yu and colleagues tried to find ways to help more patients with cancer benefit from immunotherapy.

“Despite the great success of immunotherapy, not all patients benefit equally,” Yu explained. “How to improve immunotherapy efficacy is an unmet challenge. We decided to explore whether some common medications would affect the efficacy of immunotherapy, which has not been investigated previously.”

To do so, researchers assessed the effects of 40 common medications that patients took while treated with immunotherapies such as antibiotics, aspirin and antihistamines. Findings demonstrated that patients who took antibiotics had an increased risk for death, while those taking aspirin had a reduced mortality risk. HRH1-specific antihistamines (medications that target a specific histamine receptor) significantly improved survival in patients, according to the study.

“Our findings not only uncover a previously unidentified link between allergy and cancer immune response, but also suggest that H1-antihistamines, many of which are over-the-counter drugs, may enhance immunotherapy efficacy in cancer patients,” Yu said.

Although findings from this study need to be tested in clinical studies before treatment recommendations can be made, Yu added that there are some important takeaways from the results.

“It is critical to choose the right antihistamines for cancer patients,” she explained “Our study indicated that only the second generation H1-antihistamines (selectively targeting histamine receptor H1), such as cetirizine (Zyrtec), loratadine (Claritin) and fexofenadine, but not first-generation antihistamines (nonselective but commonly used in clinical practice, including Benadryl), was associated (with) improved outcomes in patients treated with immune checkpoint inhibitors.”

Study results also demonstrated that patients with cancer who received immunotherapies, not chemotherapies, benefitted from HRH1-specific antihistamines. In addition, patients with significantly higher plasma histamine levels were more likely to respond poorly to immunotherapy and may highlight a patient group that may benefit from HRH1-antihistamine treatment. Yu said despite these important takeaways, which serve as a jumping point, more research is needed in this area.

“Our study only uncovered a tip of the iceberg on the relationships between the allergic response and cancer,” Yu explained. “We will continue to explore the relationship between the two diseases. It will be interesting to test whether (the) histamine/HRH1 axis may also induce resistance to other types of immunotherapies.”

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