Endothelial activation and stress index (EASIX) is a reliable predictor for overall survival in patients with multiple myeloma

Abstract

Background: Recently, the endothelial Activation and Stress Index (EASIX) score has been reported to predict overall survival (OS) after allogeneic stem cell transplantation. This study evaluated the prognostic role of EASIX score in patients with newly diagnosed multiple myeloma (MM). Methods: This retrospective study analyzed the records of 1177 patients with newly diagnosed MM between February 2003 and December 2017 from three institutions in the Republic of Korea. Serum lactate dehydrogenase (LDH), creatinine, and platelet count at diagnosis were measured in all included patients. EASIX scores were calculated using the formula-LDH (U/L) × Creatinine (mg/dL) / platelet count (10 9 /L) and were evaluated based on log2 transformed values. Results: The median age of patients was 63 years (range, 22-92), and 495 patients (42.1%) underwent autologous stem cell transplantation (ASCT). The median log2 EASIX score at diagnosis was 1.1 (IQR 0.3-2.3). Using maximally selected log-rank statistics, the optimal EASIX cutoff value for OS was 1.87 on the log2 scale (95% CI 0.562-0.619, p < 0.001). After median follow-up for 50.0 months (range, 0.3-184.1), the median OS was 58.2 months (95% CI 53.644-62.674). Overall, 372 patients (31.6%) showed high EASIX scores at diagnosis, and had significantly inferior OS compared to those with low EASIX (log2 EASIX ≤1.87) (39.1 months vs. 67.2 months, p < 0.001). In multivariate Cox analysis, high EASIX was significantly associated with poor OS (HR 1.444, 95% CI 1.170-1.780, p = 0.001). In the subgroup analysis of patients who underwent ASCT, patients with high EASIX showed significantly inferior OS compared to those with low EASIX (52.8 months vs. 87.0 months, p < 0.001). In addition, in each group of ISS I, II, and III, high EASIX was associated with significantly inferior OS (ISS 1, 45.2 months vs. 76.0 months, p = 0.001; ISS 2, 42.3 months vs. 66.5 months, p = 0.002; ISS 3, 36.8 months vs. 55.1 months, p = 0.001). Conclusion: EASIX score at diagnosis is a simple and strong predictor for OS in patients with newly diagnosed MM.

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019

“…EASIX was initially developed by Luft et al as a predictor of survival in patients with acute GVHD after allo-HSCT (8) and later validated to predict mortality related to different post-HSCT complications (10)(11)(12)(13)(14)(15). For the development of EASIX, the authors chose three laboratory parameters that were part of the classical diagnostic criteria of thrombotic microangiopathy (creatinine, lactate dehydrogenase, and thrombocyte counts) due to both their simplicity and their association with endothelial dysfunction and microangiopathy (8).…”

“…In the last years, EASIX has also been validated as a predictor for the development of other allo-HSCT complications, including non-relapse mortality ( 10 , 11 ), fluid overload ( 12 ), and sinusoidal obstruction syndrome ( 13 ). This score has also been validated in other hematological malignancies outside of the HSCT setting ( 14 , 15 ).…”

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

“…In conclusion, EASIX is a readily available indicator of actual endothelial dysfunction throughout the whole peritransplant period. Its applicability in non-transplant clinical settings, such as prognostication of lower risk myelodysplastic syndromes [ 73 ], multiple myeloma [ 74 ], CAR-T cell therapy, chronic heart disease, and COVID-19 is currently being explored.…”

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

“…Indeed, EASIX measured at onset of acute GVHD, on the day of transplantation, and even before starting the conditioning therapy for allogeneic stem cell transplantation predicted risk of mortality, as well as endothelial complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) and early fluid overload (22)(23)(24)(25)(26). EASIX also associated with mortality of lower and intermediate risk patients with myelodysplastic syndromes (27), and with mortality of multiple myeloma patients (28). EASIX is therefore a validated marker of endothelial risk both in immune mediated and malignant diseases.…”