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Are Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma Common?

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Key Points

  • Cardiovascular adverse events occurred in 51% of patients receiving carfilzomib and 17% of those receiving bortezomib.
  • Cardiovascular adverse events were associated with poorer prognosis.

In a study reported in the Journal of Clinical Oncology, Cornell et al found that cardiovascular adverse events are common in patients receiving proteasome inhibitor therapy for relapsed multiple myeloma and are associated with poorer outcome.

The prospective observational study involved 95 patients receiving carfilzomib-based (n = 65) or bortezomib-based (n = 30) therapy at Vanderbilt University Medical Center and the University of Pennsylvania Abramson Cancer Center between September 2015 and March 2018. Patients were assessed at regular intervals for cardiac biomarkers, including troponin I or T, brain natriuretic peptide (BNP), and N-terminal proBNP, and with electrocardiogram and echocardiography. Patients were followed for the development of cardiovascular adverse events over 18 months.

Risk of Cardiovascular Adverse Events

Median follow-up was 25 months. Overall, 64 cardiovascular adverse events occurred, with 55% being of grade ≥ 3. Cardiovascular adverse events occurred in 51% of patients receiving carfilzomib and 17% of those receiving bortezomib (P = .002). The median time to first event was 31 days, with 86% of cases occurring within the first 3 months of treatment.

Among patients receiving carfilzomib, risk of cardiovascular adverse events was higher in those with elevated baseline natriuretic peptides consisting of BNP level > 100 pg/mL or N-terminal proBNP level > 125 pg/mL (odds ratio [OR] = 10.8, P < .001). Elevation of natriuretic peptides during mid–first cycle of treatment with carfilzomib were also associated with increased risk of cardiovascular adverse events (OR = 36.0, P < .001).

Further Associations

Patients with cardiovascular adverse events had poorer progression-free survival (P = .01) and overall survival (P < .001) vs those without cardiovascular adverse events. Proteasome inhibitor therapy was safely resumed in 89% of patients, with chemotherapy modifications required in 41%.

The investigators concluded, “Cardiovascular adverse events are common during [proteasome inhibitor] therapy for relapsed [multiple myeloma], especially with carfilzomib, particularly within the first 3 months of therapy. Cardiovascular adverse events were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of cardiovascular adverse events; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.”

Robert F. Cornell, MS, MD, of the Division of Hematology and Oncology, Vanderbilt University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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