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Incidence and Management of Carfilzomib-induced Cardiovascular Toxicity; A Systematic Review and Meta-analysis

[ Vol. 21 , Issue. 1 ]

Author(s):

Azka Latif *, Vikas Kapoor , Noman Lateef , Muhammad J. Ahsan , Rana M. Usman , Saad U. Malik , Naqib Ahmad , Nathaniel Rosko , Joslyn Rudoni , Preethi William, Jack Khouri and Faiz Anwer   Pages 30 - 45 ( 16 )

Abstract:


Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta- analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib.

Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%.

Results: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and highgrade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively).

Conclusion: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hypertension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib to recognize and treat baseline cardiovascular risk factors in such patients.

Keywords:

Carfilzomib, multiple myeloma, kyprolis, PX-171, cardiotoxicity hypertension, cardiac ischemia.

Affiliation:

CHI Health, Creighton University, Omaha, NE 68178, CHI Health, Creighton University, Omaha, NE 68178, CHI Health, Creighton University, Omaha, NE 68178, CHI Health, Creighton University, Omaha, NE 68178, Internal Medicine Residency Program, University of Tennessee, Memphis, TN 37996, Department of Epidemiology and Biostatistics at the Mel and Enid Zuckerman College of Public Health., University of Arizona, Tucson, AZ 85721, Taussig Cancer Center Research, Cleveland Clinic, Cleveland, OH 44195, Department of Pharmacy, Cleveland Clinic, Cleveland, OH 44195, Department of Pharmacy, Cleveland Clinic, Cleveland, OH 44195, Department of Medicine, Division of Cardiology, University of Arizona, Tucson, AZ 85724, Department of Hematology and Oncology, Stem Cell Transplantation, Myeloma program, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, Department of Hematology and Oncology, Stem Cell Transplantation, Myeloma program, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195

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