Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL

Abstract

N-terminal natriuretic peptide type B (NTproBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n ‫؍‬ 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P ‫؍‬ .01). The reduction of NTproBNP was greater in patients (n ‫؍‬ 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P ‫؍‬ .

Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

“…One very important role of natriuretic peptides that was not addressed in the present study is monitoring improvement or progression of cardiac dysfunction after chemotherapy [4,5]. Further studies are warranted to define this role in patients with renal failure and in those in whom eGFR varies substantially during the follow-up.…”

“…In our studies on NT-proBNP patients in dialysis were excluded [2,4,5] and, although subjects with advanced renal failure were included in the Mayo Clinic series (median creatinine 1.2 mg dL 21 , range: 0.4-14.6 mg dL 21 ), the prognostic value of NT-proBNP was not separately tested in the subgroup with renal insufficiency [3]. Thus, at present, it is uncertain whether the use of NT-proBNP as a diagnostic and prognostic marker in AL amyloidosis can be extended to patients with reduced glomerular filtration rate.…”

Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide

“…We have previously reported that the suppression of the synthesis of the amyloidogenic light chain translates into rapid reduction of NT-proBNP with survival benefit in the majority of patients [12]. The dramatic downhill course of patients with amyloid cardiomyopathy indicates that rapidly acting chemotherapy regimens are required to improve survival.…”

“…A >30% reduction of serum NT-proBNP concentration was considered a clinically significant improvement of cardiac dysfunction. This threshold was chosen considering the biological variability of NT-proBNP and because it was reported to translate into a survival advantage in patients with AL amyloidosis [12]. Treatment was discontinued in patients who achieved CR, in case of toxicity, or after completion of cycle 9.…”

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

“…42 The parallel reduction of FLC and cardiac biomarkers is associated with extended survival. 23,43 As a general rule, the deeper the hematologic response, the greater the likelihood of organ response. Occasionally, the achievement of a PR translates into a significant organ response, suggesting that the toxicity and fibrillar potential of the iFLC was dependent on a threshold concentration.…”