Cancer chemotherapy and pharmacology · 2016
Effects of elotuzumab on QT interval and cardiac safety in patients with multiple myeloma.
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Passey Chaitali, Darbenzio Raymond, Jou Ying-Ming, Lynch Mark, Gupta Manish
Аннотация
PURPOSE: To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety.
METHODS: Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (treatment cycles 1-3). ECG intervals and changes relative to baseline were assessed. The key ECG endpoint was change from baseline in QT interval corrected with Fridericia's method (ΔQTcF). The relationship between elotuzumab concentration and ΔQTcF was assessed using time-matched ΔQTcF data and linear regression. Adverse events (AEs) potentially related to abnormal ECG findings were summarized.
RESULTS: There was no trend of change from baseline in QTcF, PR and QRS intervals among all 31 evaluable patients from Study CA204011, and no patient assessed had a QTcF interval >480 ms or a ΔQTcF >60 ms. Concentration-response modeling indicated that there was no significant relationship between ΔQTcF and elotuzumab serum concentration: Upper limits of 90% confidence intervals for mean change in QTcF were <10 ms over the range of observed elotuzumab concentrations. No ECG-assessed patient had an AE associated with abnormal ECG findings potentially related to proarrhythmia.
CONCLUSIONS: Study CA204011 ECG data indicate that elotuzumab treatment was not associated with QT/QTc prolongation. Concentration-response modeling demonstrated that baseline-adjusted QTcF changes did not cross thresholds for clinical or regulatory concern.
METHODS: Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (treatment cycles 1-3). ECG intervals and changes relative to baseline were assessed. The key ECG endpoint was change from baseline in QT interval corrected with Fridericia's method (ΔQTcF). The relationship between elotuzumab concentration and ΔQTcF was assessed using time-matched ΔQTcF data and linear regression. Adverse events (AEs) potentially related to abnormal ECG findings were summarized.
RESULTS: There was no trend of change from baseline in QTcF, PR and QRS intervals among all 31 evaluable patients from Study CA204011, and no patient assessed had a QTcF interval >480 ms or a ΔQTcF >60 ms. Concentration-response modeling indicated that there was no significant relationship between ΔQTcF and elotuzumab serum concentration: Upper limits of 90% confidence intervals for mean change in QTcF were <10 ms over the range of observed elotuzumab concentrations. No ECG-assessed patient had an AE associated with abnormal ECG findings potentially related to proarrhythmia.
CONCLUSIONS: Study CA204011 ECG data indicate that elotuzumab treatment was not associated with QT/QTc prolongation. Concentration-response modeling demonstrated that baseline-adjusted QTcF changes did not cross thresholds for clinical or regulatory concern.