Cardiac Repolarization After Daratumumab Monotherapy for Smoldering Multiple Myeloma
Posted: Wednesday, March 17, 2021
Treatment with the CD38-targeting monoclonal antibody daratumumab could potentially affect cardiac function in patients with smoldering multiple myeloma. Ajai Chari, MD, PhD, of the Mount Sinai School of Medicine, New York, and colleagues conducted a substudy of the multicenter phase II CENTAURUS trial to investigate the potential effect of intravenous daratumumab monotherapy on the corrected QT (QTc) interval prolongation and other electrocardiographic parameters. The results were published in Advances in Therapy.
“Analysis of electrocardiogram intervals and concentration-QTc relationships showed a small but clinically insignificant effect [on] daratumumab,” the investigators commented. “The small increase in the QT interval corrected by Fridericia’s formula [QTcF] observed in this substudy was of [a] similar magnitude to that reported for many other approved oncologic therapies.”
A total of 123 patients with intermediate- or high-risk disease were randomly assigned in a 1:1:1 ratio to receive 16 mg/kg of intravenous daratumumab monotherapy with an intense, intermediate, or short dosing schedule. Of this patient population, 31 were enrolled in the substudy. Triplicate electrocardiographic recordings were performed at screening as well as after one and eight doses of daratumumab.
Daratumumab seemed to produce a small increase in heart rate; however, the significance was unclear. Based on the results of both time-matched time-point and pharmacokinetic-pharmacodynamic analyses, there appeared to be a small but clinically insignificant effect on the QTc interval. The primary analysis showed a maximum mean increase of 9.1 ms in the QTcF. The primary pharmacokinetic-pharmacodynamic analysis predicted a maximum QTcF increase of 8.5 ms. According to the investigators, no patients had an abnormal U wave, a new QTcF of greater than 500 ms, or a change from baseline in the QTcF greater than 60 ms.
Disclosure: For full disclosures of the study authors, visit link.springer.com.