Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER‐Medicare database

Abstract

BACKGROUND: Carfilzomib improves survival in patients with recurrent myeloma. Given the strict eligibility criteria in clinical trials, the actual frequency of cardiac adverse events (CAEs) and pulmonary adverse events (PAEs) and the risk factors associated with these AEs in the general population need to be established. METHODS: The authors extracted myeloma cases in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2013 and corresponding claims through 2014. They then identified patients who received carfilzomib during their disease course. Subsequently, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify all the codes for CAEs, PAEs, and respiratory infections associated with carfilzomib use. Preexisting diagnoses corresponding to the CAEs and PAEs of interest were excluded to distinguish toxicity from comorbidity. Multivariate Cox regression was performed to determine those variables independently associated with the development of CAEs and PAEs. RESULTS: Of the 635 patients analyzed, the median age was 72 years (range, 36-94 years); 55% of the patients were male and 79% were white. The median duration of carfilzomib treatment was 58 days (range, 1-716 days). Overall, approximately 66% of the patients had codes for either CAEs or PAEs. In terms of CAEs, approximately 22% of patients developed hypertension, 15% developed peripheral edema, and 14% experienced heart failure. With regard to PAEs, approximately 28% of patients developed dyspnea, 15% developed cough, and 15% developed pneumonia. Only chronic obstructive pulmonary disease (COPD) was found to be independently associated with the development of CAEs. Patients with preexisting COPD were found to have a 40% increase in their hazard of developing CAEs (adjusted hazard ratio, 1.40; 95% CI, 1.03-1.90). CONCLUSIONS: In older adults with myeloma who are undergoing treatment with carfilzomib, new cardiac and pulmonary diagnoses were common. Patients with preexisting COPD were found to be at an increased risk of developing CAEs. Cancer 2020;126:808-813.

Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States

“…With further data mining in different subpopulations, cardiac failure was over-reported in all subgroups. Data from a recent meta-analysis included four phase III RCTs also supports the elevated risk of cardiac failure secondary to carfilzomib usage ( 32 ).…”

Onco-hypertension: Overview of hypertension with anti-cancer agents

“…All proteasome inhibitors have been associated with multiple cardiovascular complications including hypertension, congestive heart failure and arrhythmias, though the association is strongest with carfilzomib. 64–66 In a phase 3 study comparing carfilzomib to bortezomib in 929 patients with multiple myeloma, 15% of patients on carfilzomib developed grade 3 or 4 hypertension while only 3% on bortezomib did. 67 Other studies have provided consistent estimates.…”

“…67 Other studies have provided consistent estimates. 64,66,68 For example, a large meta-analysis of 24 prospective trials, including 2594 patients, found that 12.2% of patients on carfilzomib developed hypertension. 69 The hypertension associated with carfilzomib may be dose dependent.…”

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma

“…In MM patients advanced age and pre-existing risk factors, such as diabetes and hypertension, increase the risk for cardiovascular (CV) disease, which is further exacerbated by MM-associated factors, such as amyloidosis and renal failure, and anti-MM treatment, in particular radiotherapy to sternal lesions, chemotherapy, such as doxorubicin, and irreversible proteasome inhibitors, in particular carfilzomib [ 123 ]. CV complications include hypertension, peripheral edema, dyspnea, ischemia, and heart failure.…”