Cardiac biomarkers for risk stratification in newly diagnosed high-risk multiple myeloma in the GMMG-CONCEPT trial

Cardiovascular adverse events (CVAE) are clinically relevant side effects during treatment with the proteasome inhibitor carfilzomib. We investigated the predictive value of cardiac biomarkers for onset of CVAE in patients with newly diagnosed high-risk multiple myeloma treated with isatuximab, carfilzomib, lenalidomide, and dexamethasone in the GMMG-CONCEPT study (NCT03104842). Patients included in this prospective, multicenter correlative study were eligible if a serum sample before treatment initiation and at ≥ 1 later study time point were available. N-terminal pro-b-type natriuretic peptide (NT-proBNP) and high-sensitive Troponin I (hsTropI) were measured using immunoassays. Time-to-event analyses were performed using Kaplan-Meier estimators and log-rank test was used for statistical analysis. Among 126 patients included in this study, 40 reported incident CVAE. No significant differences were observed for age, sex, cardiovascular risk factors and cardiovascular comorbidities between patients who experienced CVAE compared to patients without CVAE. NT-proBNP levels were elevated at baseline in 96 (76%) patients. Neither baseline levels nor change in NT-proBNP level during early induction cycles were predictive for the occurrence of CVAE. In contrast, elevation of hsTropI above the 99th percentile was rare. Patients with hsTropI level ≥ 2.9 ng/L, corresponding to the lower limit of quantification, showed a higher risk for CVAE compared to patients with hsTropI < 2.9 ng/L at baseline (p = 0.0023). In conclusion, in patients with newly diagnosed high-risk multiple myeloma undergoing carfilzomib-based quadruplet treatment, low hsTropI pretreatment levels are of high negative predictive value for the occurrence of CVAE whereas elevated NT-proBNP levels are very common before treatment initiation.