Caution the arrhythmia association with antibody-drug conjugates: a pharmacovigilance study.

Abstract

Arrhythmias associated with antibody-drug conjugates (ADCs) are rare but potentially life-threatening adverse events (AEs). No study has systemically compared arrhythmias associations for various marketed ADCs. This needs to be clarified to guide antitumor therapies. We extracted data of patients treated with ADCs registered between 2004 q1 and 2020 q3 from the US Food and Drug Administration adverse event reporting system (FAERS). The medical dictionary for regulatory activities was used to identify arrhythmias cases. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR) with corresponding 95% confidence intervals (95% CI). Clinical characteristics of patients with ADCs-associated arrhythmias and the time to onset of arrhythmias following different ADCs were collected. A total of 140 reports were considered after inclusion criteria were used. Exposure to gemtuzumab ozogamicin (2.23, 1.67-2.97; 48 cases) and brentuximab vedotin (1.27, 1.00-1.61; 67 cases) were associated with a positive signal of arrhythmia. The highest number of arrhythmia reports was for brentuximab vedotin (n = 67). Also 88.00% of arrhythmia occurred within 60 days for all these ADCs. Arrhythmia was commonly reported in patients with hematologic tumors and breast cancer. In the time to onset of adverse events after administration, brentuximab vedotin was significantly earlier than gemtuzumab ozogamicin (38.21 vs. 40.50 days; P = 0.0093), and gemtuzumab ozogamicin was significantly earlier than trastuzumab emtansine (40.50 vs. 147.50 days; P = 0.0035). We reviewed arrhythmia adverse drug reactions associated with ADCs from the FAERS database. This study is practical for clinicians to enhance the management of arrhythmia associated with ADCs and improve ADCs treatment safety.