Real‐world experience of carfilzomib‐associated cardiovascular adverse events: SEER‐Medicare data set analysis

Abstract

Carfilzomib was approved for the treatment of multiple myeloma in 2012 and since then there have been concerns for cardiovascular toxicity from its use. With this study, we aim to further study the hazards and underlying risk factors for cardiovascular adverse events associated with carfilzomib. This study was conducted using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data set of multiple myeloma from 2001 to 2015. Data were analyzed for hazards ratio of cardiovascular adverse events between carfilzomib users and nonusers. We identified 7330 patients with multiple myeloma of whom 815 were carfilzomib users. Carfilzomib users had a statistically significant hazard ratio of 1.41 with p < 0.0001 for all cardiovascular adverse events as compared to nonusers. Carfilzomib use was significantly associated with increased risk of heart failure (HR 1.47, p = 0.0002), ischemic heart disease (HR 1.45, p = 0.0002), and hypertension (HR 3.33, p < 0.0001), whereas there was no association between carfilzomib use and cardiac conduction disorders (arrhythmia and heart blocks). Carfilzomib users were at higher risk of new‐onset edema (HR 5.09, p < 0.0001), syncope (HR 4.27, p < 0.0001), dyspnea (HR 1.33, p < 0.0001), and chest pain (HR 1.18, p < 0.0001) as compared to carfilzomib nonusers. Age above 75 years, preexisting cardiovascular disease, obesity, and twice a week carfilzomib schedule were significant risk factors associated with cardiovascular adverse events in carfilzomib users. The median time of the onset for all cardiovascular adverse events was 3.1 months. This study has identified a significantly higher likelihood of cardiovascular adverse events in elderly Medicare patients receiving carfilzomib.

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.…”

Current Desensitization Strategies in Heart Transplantation

“…Both bortezomib and carfilzomib carry distinct, but not insignificant side-effect profiles, the former being associated with peripheral neuropathy while the latter, based on the myeloma literature, carries a theoretical risk of cardiotoxicity ( 140 , 142 ). The magnitude of risk in heart transplant candidates is unknown and must be balanced with the potential benefits given the ultimate goal.…”

Treatment of double-refractory multiple myeloma

“…Частота специфических для карфилзомиба неже лательных явлений (≥III степени тяжести) на фоне терапии Kd70 была невысока и для сердечной недо статочности составила 2,9 %, для артериальной ги пертензии -6,0 % и для ишемической болезни сер дца -0,84 % [16]. Согласно данным американского эпидемиологического регистра SEER риск сердечно сосудистых осложнений увеличивают возраст стар ше 75 лет, предшествующая патология сердца и со судов, ожирение и режим введения карфилзомиба 2 раза в неделю по сравнению с введением 1 раз в неделю [18].…”