Cardiovascular (CV) adverse events were common in patients receiving proteasome inhibitor therapy for relapsed multiple myeloma, especially with carfilzomib-based therapy, according to results from the PROTECT study.
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While prior studies have shown an increased risk for CV toxicities with proteasome inhibitor therapy, detailed descriptions of the events and risk factors have been lacking. “Furthermore, there is no validated protocol to help determine which patients are at highest risk of CV toxicity during therapy, nor is there management guidance for patients who experience a [CV adverse event],” wrote Robert F. Cornell, MD, of Vanderbilt University, Nashville, Tenn., and colleagues in the Journal of Clinical Oncology.
The PROTECT (Prospective Observation of Cardiac Safety with Proteasome Inhibitor) study was conducted at Vanderbilt University Medical Center and the University of Pennsylvania Abramson Cancer Center, Philadelphia, between September 2015 and March 2018.
Researchers followed 95 patients with relapsed multiple myeloma who were treated with either bortezomib or carfilzomib for a total duration of 18 months. A total of 65 patients received a carfilzomib-based therapy and 30 patients received a bortezomib-based therapy.
Study patients received a CV assessment at baseline and at the beginning of each treatment cycle for the initial six cycles of proteasome inhibitor therapy. Subsequently, patients were monitored for the development of CV adverse events. CV assessments included ECG, echocardiography, and measurement of other cardiac biomarkers, such as NTproBNP and troponin I or T.
CV toxicities were reported among 5 patients (16.7%) of patients treated with bortezomib and 33 patients (50.7%) treated with carfilzomib (P = .005).
In total, there were 64 CV adverse events reported, most of which were grade 2 or 3, and 56 of which occurred while on carfilzomib-based therapy. For carfilzomib, the most common complications were heart failure (23 cases), followed by grade 3 or 4 hypertension (13 cases). Cardiac chest pain, atrial fibrillation, and acute coronary syndrome were reported in fewer cases.
The researchers also found that elevated natriuretic peptides that occurred before starting carfilzomib therapy or within the first 3 weeks of carfilzomib therapy were associated with a substantially higher risk of CV adverse events.
Patients who have multiple CV risk factors, and especially patients with a history of CV complications and elevated baseline natriuretic peptides, should be referred for a comprehensive cardiac evaluation, the researchers advised. “Such patients are at highest risk of CV [adverse events] with carfilzomib-based therapy, and optimization of CV therapy seems to improve overall care, allow continuation of potentially lifesaving cancer treatment, and affect severity or development of CV [adverse events],” they wrote.
A key limitation of the study was the lack of standardized treatment regimens. As a result, there was a broad dosing range for carfilzomib, in comparison to bortezomib.
Some authors reported financial relationships with carfilzomib maker Amgen and bortezomib maker Takeda, as well as with other companies.
SOURCE: Cornell RF et al. J Clin Oncol. 2019 Jun 12. doi: 10.1200/JCO.19.00231.