Adverse event profiles of four monomethyl auristatin E-conjugated antibody drug conjugates: a disproportionality analysis based on the US FDA adverse event reporting system (FAERS) database.

Background: Antibody-drug conjugates (ADCs) with monomethyl auristatin E (MMAE) have recently become prevalent in cancer treatment. This study aimed to comprehensively examine the adverse events (AEs) associated with regulatory-approved MMAE-conjugated ADCs using the FDA Adverse Event Reporting System (FAERS).

Research design and methods: A disproportionality analysis of reports from July 2011 to September 2024 was conducted to detect AE signals in adult patients with cancer receiving any of the four MMAE-conjugated ADCs (brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin) using reporting odds ratio and information component.

Results: FAERS yielded 12,655 reported cases with 4,958 drug-AE pairs. Positive signals observed across the four MMAE-ADCs included 'blood and lymphatic system disorders' and 'metabolism and nutrition disorders' at the system organ class, and anemia, febrile neutropenia, hypokalemia, peripheral neuropathy, and pneumonitis for individual AEs, with 54 other overlapping AEs shared by at least three of the ADCs.

Conclusions: FAERS analysis revealed overlapping safety signals in MMAE-conjugated ADCs. Although further research is necessary to clarify the causal relationships, our findings provide a basis for understanding the characteristics of possible AEs in MMAE-ADCs, aiding clinical decision-making for patient safety management.