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Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

ABSTRACT: Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting 'CVAEs risk score' distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

SUBMITTER: Astarita A

PROVIDER: S-EPMC8036868 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

Astarita Anna A Mingrone Giulia G Airale Lorenzo L Vallelonga Fabrizio F Covella Michele M Catarinella Cinzia C Cesareo Marco M Bruno Giulia G Leone Dario D Giordana Carlo C Cetani Giusy G Salvini Marco M Gay Francesca F Bringhen Sara S Rabbia Franco F Veglio Franco F Milan Alberto A

Cancers 20210401 7

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood ...[more]

PMID: 33915804

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Project description:BackgroundMultiple myeloma (MM) is the second most common hematological malignancy, and the treatments markedly elevate the survival rate of the patients in recent years. However, the prevalence of cardiovascular adverse events (CVAEs) in MM had been increasing recently. CVAEs in MM patients are an important problem that we should focus on. Clinical tools for prognostication and risk-stratification are needed.Patients and methodsThis is a retrospective study that included patients who were newly diagnosed with multiple myeloma (NDMM) in Shanghai Changzheng Hospital and Affiliated Jinhua Hospital, Zhejiang University School of Medicine from June 2018 to July 2020. A total of 253 patients from two medical centers were divided into training cohort and validation cohort randomly. Univariable analysis of the baseline factors was performed using CVAEs endpoints. Multivariable analysis identified three factors for a prognostic model that was validated in internal validation cohorts.ResultsFactors independently associated with CVAEs in NDMM were as follows: age>61 years old, high level of baseline office blood pressure, and left ventricular hypertrophy (LVH). Age contributed 2 points, and the other two factors contributed 1 point to a prognostic model. The model distinguished the patients into three groups: 3-4 points, high risk; 2 points, intermediate risk; 0-1 point, low risk. These groups had significant difference in CVAEs during follow-up days in both training cohort (p<0.0001) and validation cohort (p=0.0018). In addition, the model had good calibration. The C-indexes for the prediction of overall survival of CVAEs in the training and validation cohorts were 0.73 (95% CI, 0.67-0.79) and 0.66 (95% CI, 0.51-0.81), respectively. The areas under the receiver operating characteristic curve (AUROCs) of the 1-year CVAEs probability in the training and validation cohorts were 0.738 and 0.673, respectively. The AUROCs of the 2-year CVAE probability in the training and validation cohorts were 0.722 and 0.742, respectively. The decision-curve analysis indicated that the prediction model provided greater net benefit than the default strategies of providing assessment or not providing assessment for all patients.ConclusionA prognostic risk prediction model for predicting CVAEs risk of NDMM patients was developed and internally validated. Patients at increased risk of CVAEs can be identified at treatment initiation and be more focused on cardiovascular protection in the treatment plan.

Project description:ImportanceCardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.ObjectiveTo determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.Data sourcesPubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017.Study selectionPhase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis.Data extraction and synthesisData were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE.Main outcomes and measuresCardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded.ResultsA total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively.Conclusions and relevanceCarfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.

Project description:BackgroundAcute myocardial infarction (AMI) remains a major cause of mortality and morbidity globally, with a high incidence of major adverse cardiovascular events (MACE) post-primary percutaneous coronary intervention (PPCI). The DETERMINE score, derived from electrocardiographic (ECG) markers, has shown promise as a predictor of adverse outcomes, but its clinical utility requires further validation.ObjectiveTo evaluate the predictive value of the DETERMINE score for MACE and provide early clinical warnings for high-risk patients.MethodsThis bidirectional cohort study included AMI patients from the Second Affiliated Hospital of Anhui Medical University between 2019 and 2023. The training cohort comprised 545 patients between January 2019 and January 2023, while the validation cohort consisted of 122 patients between February 2023 and July 2023. The primary endpoint was MACE within one-year post-PPCI. The relationship between the DETERMINE score and MACE was analyzed using Cox regression, trend tests, and restricted cubic splines to assess linear and nonlinear associations. Patients were stratified into risk groups based on tertiles or optimal cutoffs, and Kaplan-Meier survival curves compared MACE incidence across groups. Predictive accuracy was evaluated through time-dependent C-index, ROC curves, decision curve analysis, and calibration, and compared to other prognostic scores, including the Selvester, GRACE, and SYNTAX scores, as well as left ventricular ejection fraction (LVEF). Subgroup analyses by sex, age, and culprit artery involvement were also conducted.ResultsCox multivariate regression indicated that the DETERMINE score was an independent risk factor for MACE (HR = 1.56, 95% CI 1.38-1.75, P < 0.001). Trend test and RCS showed a positive correlation and non-linear relationship between the DETERMINE score and MACE (P-trend < 0.001, P-overall < 0.001, P-nonlinear: 0.003). Kaplan-Meier survival analysis revealed that, in both the training and validation datasets, groups with a higher DETERMINE score showed a higher cumulative risk of MACE. The DETERMINE score outperformed traditional prognostic scores (Selvester, GRACE, SYNTAX) in terms of predictive accuracy, with an AUROC of 0.840 at 12 months in the training cohort. The score also provided a substantial clinical net benefit, particularly over longer follow-up periods. Subgroup analyses confirmed its predictive power across different demographics and clinical presentations.ConclusionThe DETERMINE score has outstanding predictive power for MACE post-PPCI, which can guide the early identification of high-risk patients with poor prognosis of AMI in clinical practice.

Dataset Information

Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

Publications

Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

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