The Impact of Antihistamines on Immunotherapy: A Systematic Review

Abstract

Cancer remains one of the most significant public health challenges globally, contributing to a substantial burden of disease across all populations. Conventional therapies of chemotherapy, radiation, and surgery are commonly used to treat all forms of cancer; however, they all have significant side effects to their use. Immunotherapy has emerged as an effective treatment type for a variety of cancers. As the benefits of immunotherapy in cancer treatment are identified, the interaction between immunotherapy and over-the-counter medication has been explored. Due to the cost and length of time to conduct clinical trials, alternative therapeutics are being examined. Recently, the potential interaction between antihistamines and immunotherapies has gained attention. Six articles were included that analyzed this association. In total 4,171 patients were analyzed with a mean age of 62.66. Cancer types vary between lung (including small-cell and non-small-cell lung cancer), melanoma, hepatobiliary, head and neck, breast, gastrointestinal, renal cell, gynecological, and colon cancers. Among all studies, checkpoint inhibitors were used as a form of immunotherapy. Two studies specifically identified which checkpoint therapies were utilized, including nivolumab, pembrolizumab, ipilimumab, and atezolizumab. All articles found a significant improvement in overall survival rates and longer progression-free rates when antihistamines were added to immunotherapy regimens compared to patients who did not utilize antihistamines. Additionally, some studies also analyzed mortality rates, and each found a significant reduction in mortality rates when antihistamines were paired with immunotherapy. The combination of antihistamines as cancer chemotherapeutics with immunotherapy represents a promising approach to the treatment of cancer. As immunotherapies continue to reshape cancer treatment and as we begin to investigate alternative uses for everyday medications, antihistamines may propose beneficial effects on improving the efficacy of immunotherapy.

Keywords: cationic amphiphilic antihistamines; first-generation antihistamines; histamine receptors; immune checkpoint therapy; immunotherapy; non-cationic amphiphilic antihistamines; second-generation antihistamines.

Figure 1. PRISMA diagram indicating the search methodology

PRISMA: preferred reporting items for systematic reviews and meta-analyses

Figure 2. Type of cancer diagnoses among the patients analyzed