Acetaminophen may reduce immunotherapy efficacy in patients with cancer
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CHICAGO — Acetaminophen suppressed antitumor immunity in a cohort of patients with cancer, according to study results presented during ASCO Annual Meeting.
Researchers recommended caution when prescribing acetaminophen among patients with cancer who are treated with immune checkpoint inhibitors.
Rationale and methods
“Acetaminophen is the first-line strategy to manage mild-to-moderate pain among patients with advanced cancer,” Antoine Italiano, MD, PhD, professor and head of the early phase trials and sarcoma units at Institute Bergonié in Bordeaux, France, said during his presentation. “However, preclinical studies have demonstrated that acetaminophen inhibits the proliferation of immune cells and the T cell-dependent antibody response. In addition, randomized studies have shown that acetaminophen has a negative impact on vaccination response, with decreased antibody levels in individuals receiving acetaminophen for fever prophylaxis.”
Italiano and colleagues sought to assess the effect of acetaminophen on the efficacy of immunotherapy among patients with cancer included in three previously published study cohorts: the CheckMate 025 trial (n = 297), the institutional biomarker program BIP (n = 34) and the institutional biomarker program PREMIS (n = 297).
Researchers additionally evaluated the immunomodulatory effects of acetaminophen on a preclinical tumor model and on human peripheral blood mononuclear cells from otherwise healthy donors.
Key findings
Researchers found patients with detectable plasma acetaminophen levels at onset of treatment with immune checkpoint inhibitors had significantly worse clinical outcomes (HR for PFS = 1.43; 95% CI, 1.07-1.91; and HR for OS = 1.78; 95% CI, 1.18-2.68), independent of age, performance status, number of previous lines of treatment, tumor type, number of metastatic sites and presence of liver metastases.
Researchers also observed decreased immune checkpoint inhibitor efficacy in the preclinical model and decreased efficacy of PD-1 blockade-associated interferon-gamma secretion by human peripheral blood mononuclear cells.
Decreased efficacy of immune checkpoint inhibitors in vivo was associated with increased tumor infiltration by regulatory T cells, and acetaminophen administered over a 24-hour period induced significant expansion of peripheral regulatory T cells among the cohort of otherwise healthy individuals.
Moreover, patients who received acetaminophen also experienced upregulation of interleukin-10 upon treatment with immune checkpoint inhibitors.
Looking ahead
“This is the first comprehensive picture of the immunomodulatory effects of acetaminophen, which showed the drug is associated with decreased efficacy of immune checkpoint inhibitors in patients with advanced cancer,” Italiano said. “Future research will examine the direct or indirect effect of the association of acetaminophen on [regulatory T cells].”
For more information:
Antoine Italiano, MD, PhD, can be reached at a.italiano@bordeaux.unicancer.fr.