Abstract
BACKGROUND: Infusion reactions (IRs) are common adverse events associated with biologics, often triggered by cytokine release from immune and tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) is a key immune mechanism in which therapeutic antibodies recruit immune effector cells, such as natural killer cells, to induce target cell lysis. This study aimed to clarify the association between activated ADCC and IRs in antitumor antibodies using the Japanese Adverse Drug Event Report (JADER) database. METHODS: Data from the JADER database (April 2004 to February 2022) were analyzed to identify IRs related to 25 antitumor antibodies. The reporting odds ratio (ROR) was calculated to assess the association between IRs and antitumor antibodies, and statistical analyses were conducted using Fisher's exact test. RESULTS: Avelumab was the only anti-PD-1/PD-L1 antibody with a significant association with IRs (ROR: 5.44, 95% confidence interval [CI]: 3.59-8.22). Antibodies with ADCC activity detected significantly more IR signals (9/14, 64.3%) than those without ADCC activity (1/11, 9.1%; p = 0.0119). CONCLUSIONS: This study suggests an association between ADCC and the occurrence of IRs in antitumor antibodies based on JADER database analysis. These findings provide valuable insights for the prevention and management of IRs.