PURPOSE: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS: Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION: CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.
PURPOSE: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS: Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION: CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.
Authors: Daniel Lenihan; Joseph Carver; Charles Porter; Jennifer E Liu; Susan Dent; Paaladinesh Thavendiranathan; Joshua D Mitchell; Anju Nohria; Michael G Fradley; Iskra Pusic; Keith Stockerl-Goldstein; Anne Blaes; Alexander R Lyon; Sarju Ganatra; Teresa López-Fernández; Rupal O'Quinn; Giorgio Minotti; Sebastian Szmit; Daniela Cardinale; Jose Alvarez-Cardona; Giuseppe Curigliano; Tomas G Neilan; Joerg Herrmann Journal: CA Cancer J Clin Date: 2020-09-10 Impact factor: 508.702
Authors: G Curigliano; D Lenihan; M Fradley; S Ganatra; A Barac; A Blaes; J Herrmann; C Porter; A R Lyon; P Lancellotti; A Patel; J DeCara; J Mitchell; E Harrison; J Moslehi; R Witteles; M G Calabro; R Orecchia; E de Azambuja; J L Zamorano; R Krone; Z Iakobishvili; J Carver; S Armenian; B Ky; D Cardinale; C M Cipolla; S Dent; K Jordan Journal: Ann Oncol Date: 2020-02 Impact factor: 32.976
Authors: Brian A Van Tine; Angela C Hirbe; Peter Oppelt; Ashley E Frith; Richa Rathore; Joshua D Mitchell; Fei Wan; Shellie Berry; Michele Landeau; George A Heberton; John Gorcsan; Peter R Huntjens; Yoku Soyama; Justin M Vader; Jose A Alvarez-Cardona; Kathleen W Zhang; Daniel J Lenihan; Ronald J Krone Journal: Clin Cancer Res Date: 2021-03-25 Impact factor: 12.531
Authors: Virginia S Hahn; Kathleen W Zhang; Lova Sun; Vivek Narayan; Daniel J Lenihan; Bonnie Ky Journal: Circ Res Date: 2021-05-13 Impact factor: 17.367