Page 249 - Haematologica May 2020

Cardiac biomarkers in Mayo stage I amyloidosis
Table 2. A comparison of patients with N-terminal pro b-type natriuretic peptide >152 ng/L versus <152 ng/L.
Other biomarkers
High-sensitive cardiac troponin T dFLC
ALP (U/L)
Cardiac magnetic resonance imaging (CMR) findings: CMR positive for amyloidosis (n=90)
Extracellular volume
Echocardiogram parameters
Echo global strain (%)
Echo lVS (mm)
NT- proBNP ≤152 g/L (n=170) 7
10.90 170
7(22%)
0.327 -21.96
10
NT-pro BNP >152 ng/L (n=208)
11 18.70 207
18(31%)
0.355 -20.34
10
P* <0.001
0.204 0.994
0.364
0.470 0.40
0.914
*Mann-Whitney U-test for non-parametric variables; Chi-squared for categorical variables. NT-pro BNP: N-terminal pro b-type natriuretic peptide; ALP: alkaline phosphatase; CMR: cardiac magnetic resonance imaging; lVS: interventricular septal thickness; dFLC: difference between involved and uninvolved serum free light chains.
Table 3. Factors included in a multivariate analysis and their significance (separate multivariate models were developed with and without cardiac magnetic resonance imaging [CMR] due to smaller patient numbers with CMR data).
Factor in multivariate analysis Age
ANS
NT-proBNP> 152 ng/L
HsTNT >10 ng/L
CMR positivity
Analysis excluding CMR findings
P/ HR (CI)
0.269/1.021(0.984-1.058)
0.624/0.696(0.164-2.962)
0.008/3.180(1.349-7.495)
0.771/0.880(0.370-2.091)
Analysis including CMR findings
0.363/0.967(0.900-1.039)
0.322/6.749(0.154-295.885)
0.918/1.074(0.999-1.154)
0.073/1.059(0.995-1.128)
0.026/5.360(1.219-23.574)
-
HR: hazard ratio; CI: confidence interval; ANS: autonomic nervous system; NT-proBNP: N-terminal pro b-type natriuretic peptide; hsTNT: high-sensitive cardiac troponin T; ImiD: immunomodulatory drug; CMR: cardiac magnetic resonance imaging.
HR: 6.563, CI: 1.689-25.492) (Figure 1D). Too few patients have sufficient follow up for meaningful longer-term sur- vival analysis at present.
Treatment details were available in 97% of cases (n=368/378) and are outlined in Table 1. A total of 91% (n=346/378) patients were treated with chemotherapy. The most common treatment given was bortezomib (mostly cyclophosphamide-bortezomib-dexamethasone) (n= 246/368, 67%) followed by thalidomide (mainly cyclophosphamide-thalidomide-dexamethasone) (n=110/369, 30%). Fifteen percent (n=55/368) of patients has an upfront autologous stem cell transplant (ASCT). Treatment type was not prognostic for survival on univari- ate analysis (Table 1).
In the 346 patients who received chemotherapy 89% (n=337/378) were evaluable at six months. Haematological response was as follows: complete response (CR) 51% (n=173/378, very good partial response (VGPR) 13% (n=46/346), partial response (PR) 3% (n=12/346), no response (NR) 4% (n=14/346) and pro- gressive disease (PD) 17% (n=58/346). The OS of patients who achieved a CR to treatment was significantly longer than those who did not achieve a CR (median OS 109 vs. 75 months, P<0.001). The six-month landmark analysis was as follows: CR- median survival not reached, non-CR median survival 88 months, P<0.001. Survival at 1 and 3 years by NT-proBNP <152 ng/L was: CR: 100%, 96% versus non-CR: 90%, 69% respectively, and for patients with NT-proBNP >152 ng/L: CR: 96%, 80% and non-CR: 91%, 53% respectively, P<0.001. A total of 95 patients had NT-proBNP >152 ng/L and achieved a CR at six
months. Of these patients, 15% (n=14/95) achieved a reduction in the invloved FLC (iFLC) to <10 mg/L at six months. There was no significant survival difference between those patients who achieved an iFLC <10 mg/L at six months versus those who did not (P=0.396). Of the 95 patients with NT-proBNP >152 ng/L who achieved a CR at six months, 8% (n=8/95) achieved a CR at one month, and 39% (n=37/95) after three months. There was no significant difference in OS between those patients who achieved a CR versus non-CR at one month (P=0.281), or three months (P=0.402).
Of the 346 patients treated, 80% (n=277/346) had NT-proBNP readings at 12 months. Based on a 30% change in NT-proBNP to define response: 32% (n=88/277) patients had reduction in their NT-proBNP levels, 50% (n=138/277) patients’ values increased and 18% (n=51/277) patients did not reach either criteria. When analysing the entire cohort there was no significant differ- ence in survival between patients who had an NT-proBNP response versus no response/ progression, (P=0.193); the 3- year survival of patients was 76% versus 70% for patients with an NT-proBNP response compared with unchanged/progression, respectively. However, when the analysis was restricted to patients with NT-proBNP >152 ng/L, outcomes were significantly poorer in the patients with a baseline NT-proBNP level of >152 ng/L who pro- gressed (P=0.001).
Multivariate models were developed using variables sig- nificant on univariate analysis, defined as a P-value <0.05, (Table 3). A model including CMR was done separately due to the limited number of patients with CMR data. On
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