Page 248 - Haematologica May 2020

F.A. Sharpley et al.
1.00
0.75 0.50
0.25 0.00
1.00
0.75 0.50
0.25 Log rank 0.00 P=0.001
NT-proBNP ≥152 NT-proBNP <152
B
1.00 0.75 0.50
0.25 Log rank 0.00 P=0.204
C
D
1.00 0.75 0.50
0.25 Log rank 0.00 P=0.007
A
N=378
Figure 1. Survival curves for Mayo stage I patients demonstrating. (A) Overall survival was not reached; overall survival at 1, 3, and 5 years was 95%, 87% and 76% respectively. (B) The impact of haematological response to treatment at six months and survival outcomes, patients achieving a complete response to treatment versus not a complete response (log rank P<0.001). (C) N-terminal pro b-type natriuretic peptide (NT-pro-BNP) above and below 152 ng/L showing poorer outcome for patients with NT-proBNP >152 ng/L, (log rank P=0.001). (D) Cardiac magnetic resonance imaging findings demonstrating a significantly poorer outcome for patients with cardiac amyloid deposition, (log P=0.007)
HR: 1.034, CI: 1.010-1.059) but using receiver operating characteristic (ROC) analysis there was no clearly identifi- able threshold for poorer outcomes. The presenting free light chains (FLC) were not prognostic for survival in this cohort as a continuous variable or a dichotomous variable above or below a difference between involved and unin- volved FLC (dFLC) of 50 mg/L or 180 mg/L (Table 1). At four years 83% versus 77% of patients with a dFLC above or below a value of 50 mg/L were alive (log rank P=0.202).
Although all the patients included in this study had no evidence of cardiac involvement, and cardiac biomarkers below the threshold for defining cardiac involvement, hsTNT and NT-proBNP were still prognostic for survival both on univariable analysis and only NT-proBNP on mul- tivariate analysis. We undertook ROC analysis to define thresholds for NT-proBNP and hsTNT, (identified as 152 ng/L and 10 ng/L respectively), as prognostic cut offs for poorer survival. The OS was significantly better for patients with NT-proBNP <152 ng/L versus those with a greater value (although median OS not reach for either group) (log rank P≤0.001; Figure 1C). At 1, 3, and 5 years, for patients with NT-proBNP below and above 152 ng/L, the OS was 96% versus 94%; 91% versus 82%; and 83% versus 70% respectively. The OS at 1, 3, and 5 years for patients with hsTNT below and above 10 ng/L was 98%% versus 93%%, 91% versus 84% and 87% versus 70% respectively. The median OS was not reached for either group. There was no significant difference in the
median creatinine or eGFR for patients with a NT-proBNP value </≥152 ng/L (P=0.091 and 0.206 respectively) ruling out impairment of renal function as a cause of abnormal NT-proBNP in this cohort.
CMR was undertaken since 2015 and results were avail- able on 90/378 (24%) patients. Twenty-eight percent (n=25/90) of patients had cardiac involvement by CMR. In the patients who had a CMR with NT-proBNP below (32 patients) and above (58 patients) 152 ng/L, the CMR was positive for amyloid deposition in 22% versus 31% of cases, respectively (P=0.353) (see Table 2). There was a trend towards higher NT-proBNP in patients with a posi- tive CMR median NT-proBNP 220 ng/L versus 169 ng/L (P=0.089) (Figure 2). The median LV wall thickness by echocardiogram (11 mm vs. 10 mm [P=0.1902]) and hsTNT values (17 ng/L vs. 14 ng/L [P=0.373]) were not sig- nificantly different in those patients with CMR positivity for amyloid deposition compared to those patients with negative CMR findings respectively. After gadolinium contrast, the extracellular volume fraction (which directly reflects myocardial interstitial expansion by amyloid dep- osition) was calculated with a median ECV of 0.33 (0.24- 0.71). The mean ECV of patients with cardiac involve- ment was 0.44 versus 0.31 (P<0.0001) for those without cardiac involvement. Cardiac involvement on CMR was prognostic for OS with the 1- and 2-year survival for patients with CMR positive versus negative being 86% ver- sus 98% and 69% versus 98% respectively (P=0.007,
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