Carfilzomib poses higher risk of CVAEs, review suggests

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).