Why carry out this study?

There are a limited number of QT studies of intravenous drugs administered over 3 h in duration.

Daratumumab, a monoclonal antibody administered intravenously, is used to treat multiple myeloma; it targets CD38, a 45-kD transmembrane glycoprotein that is highly expressed on myeloma cells.

CD38 is also expressed on cardiomyocytes, and daratumumab therapy may have an effect on patient cardiac function; therefore, a QTc substudy was conducted using patients from the phase 2 CENTAURUS study, which evaluated daratumumab 16 mg/kg administered intravenously in patients with intermediate- or high-risk smoldering multiple myeloma.

What was learned from the study?

Primary time-matched time-point and pharmacokinetic-pharmacodynamic analyses showed a small but clinically insignificant effect of daratumumab monotherapy on QTc in patients with intermediate- or high-risk smoldering multiple myeloma, which was confirmed in pre-specified sensitivity analyses.

The small increase in QTcF observed in this substudy was of similar magnitude to that reported for many other approved oncologic therapies.