Bortezomib-Induced Perimyocarditis in a Multiple Myeloma Patient: A Case Report

Abstract

Bortezomib (BTZ) is a proteasome inhibitor used in the treatment of multiple myeloma (MM) and other hematological malignancies. Although carfilzomib, a second-generation proteasome inhibitor, is most strongly associated with cardiotoxicity, BTZ has been associated with several cardiovascular complications including congestive heart failure, arrhythmias, and rarely myocarditis. Here, we report the first case of a BTZ-induced perimyocarditis. The patient was a 40-year-old woman with recently diagnosed MM who was admitted to the hospital with syncope at the start of her second cycle of induction therapy with BTZ, lenalidomide, and dexamethasone. She had a witnessed syncopal event in the emergency room with the telemetry showing sustained ventricular tachycardia. Laboratory workup showed elevated N-terminal pro B-type natriuretic peptide and normal troponin I. Transthoracic echocardiogram (TTE) showed a low ejection fraction of 40% with global hypokinesis of the left ventricle and trace pericardial effusion. Cardiac magnetic resonance imaging with gadolinium was consistent with acute myocarditis. The patient had recurrent pleuritic chest pain, and a repeat TTE showed worsening pericardial effusion consistent with pericarditis. Endomyocardial biopsy was done which showed nonspecific myocyte hypertrophy and foci of fibrosis, but was negative for giant cell myocarditis, hemochromatosis, and amyloidosis. Extensive infectious disease workup ruled out known infectious causes for perimyocarditis. Given the close timing between BTZ treatment (5 subcutaneous doses with a cumulative dose of 6.5 mg/m<sup>2</sup>), the absence of other iatrogenic or infectious causes, and probable or likely association with BTZ as assessed by the validated causality assessment scoring tools, it was concluded that the acute perimyocarditis was secondary to BTZ exposure. Here, we report the first case of BTZ-induced perimyocarditis and discuss the incidence and pathophysiology of BTZ-cardiovascular toxicity.

Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors

“…Although bortezomib and ixazomib mediate reversible inhibition, only bortezomib, as reported in previous observational studies [8][9][10], showed adverse event signals for multiple CAEs (Table 1). Carfilzomib, an irreversible PI, has previously been demonstrated to have a high risk of CAEs in a database study that compared all drugs [2].…”

“…No previous report has examined the risk of developing CAEs when compared with anticancer drugs with potential CAE concerns. Bortezomib has also been reported to cause cardiotoxicity, including cardiac failure, ischemic cardiac disease, and arrhythmias [8][9][10]. Furthermore, evidence on the risk of ixazomib-induced CAEs is limited to a few reports [11].…”

Recent Advances in Serum Biomarkers for Cardiological Risk Stratification and Insight into the Cardiac Management of the Patients With Hematological Malignancies Treated With Targeted Therapy

“…Similarly, Alali and Baljevic reported a case of peri myocarditis induced by bortezomib in a patient with multiple myeloma. The patient's laboratory results revealed elevated N-terminal pro-B-type natriuretic peptide levels and normal troponin I levels [ 91 ].…”

Myocarditis in Cancer Patients: A Review of an Emerging Problem in Cardio-Oncology

“…Proteasome inhibitors, such as car filzomib and bortezomib, and immunomodulators, such as lenalidomide, are used for the treatment of various hematologic malignancies, including multiple myeloma (MM), mantle cell lymphoma, systemic light-chain amyloidosis, T-cell lymphoma, and Waldenstrom macroglobulinemia / lymphoplasmacytic lymphoma, among others (Figure 1). 28 The proteasome plays an important role in maintaining cardiac protein homeostasis and protein quality in myocytes, preserving cell mass, and controlling sarcomere quality. Inhibition of proteasomal activity thus leads to a buildup of misfolded proteins, which can result in cell apoptosis, inflammation, and acute myopericarditis.…”

“…Inhibition of proteasomal activity thus leads to a buildup of misfolded proteins, which can result in cell apoptosis, inflammation, and acute myopericarditis. 28 Eosinophilic myocarditis is a rare condition occurring secondary to treatment with lenalidomide. As the name implies, it results from an inflammatory process with eosinophil infiltration of the myocardium.…”