Cardiac and renal complications of carfilzomib in patients with multiple myeloma

Abstract

Clinical trials with carfilzomib have indicated a low but reproducible incidence of cardiovascular and renal toxicities. Among 60 consecutive myeloma patients treated with carfilzomib-based regimens who were thoroughly evaluated for cardiovascular risk factors, 12% (95% confidence interval, 3.8%-20%) experienced a reversible reduction of left ventricular ejection fraction (LVEF) by ≥20%, an objective measure of cardiac dysfunction. The incidence of LVEF reduction was 5% at 3 months, 8% at 6 months, 10% at 12 months, and 12% at 15 months, whereas the respective carfilzomib discontinuation rate unrelated to toxicity was 17%, 35%, 41%, and 49%. The presence of any previously known cardiovascular disease was associated with an increased incidence of cardiac events (23.5% vs 7%; P = .07), but there was no association with the dose of carfilzomib or the duration of infusion. Re-treatment with carfilzomib at lower doses was possible. Carfilzomib was commonly associated with a transient reduction of estimated glomerular filtration rate (eGFR) but also improved renal function in 55% of patients with baseline eGFR <60 mL/min/1.73 m2. Further investigation is needed to elucidate the underlying mechanisms of carfilzomib-related cardiorenal toxicity.

Conflict of interest statement

Conflict-of-interest disclosure: M.A.D. received honoraria from Celgene, Janssen, Takeda, and Amgen. E.T. received honoraria from Medtronic, Celgene, Janssen, and Amgen. E.K. received honoraria from Janssen, Takeda, and Amgen. The remaining authors declare no competing financial interests.

Figures

Graphical abstract

Figure 1.

Incidence of cardiac events in patients treated with carfilzomib. Cumulative incidence function estimates of cardiac events and discontinuation because of progressive disease or for other (nontoxicity) reasons.