The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis

Abstract

In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit. (Blood. 2010; 116(18):3426-3430)

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

“…22 The presence and character of cardiac involvement at diagnosis remains a major prognostic factor for all AL patients; indeed, it appears that all AL patients have a degree of cardiac involvement at diagnosis even if asymptomatic. 23,24 Cardiac events are the most common cause of death in AL patients. Patients with cardiac involvement can present with fatigue, progressive dyspnea on exertion, diastolic dysfunction, left ventricular hypertrophy in the absence of hypertension or valvular disease, pericardial effusion, and low voltage on electrocardiogram.…”

“…Re-examinations of overall prognostic approaches to newly diagnosed patients continue to emerge, including ones that employ variables related to new cardiac biomarkers and to the plasma-cell disease in AL such as cyclin D1 expression levels in clonal plasma cells and the numerical difference between iFLC and uninvolved FLCs (Table 1). 17,23,28 These retrospective efforts are particularly useful for the interpretation of phase II clinical trial results in the newly diagnosed when prognostic data are available but, as survival improves with new treatments and as new diagnostics become available, they must continue to be updated.…”

“…An appreciation of factors that potentially affect biomarker levels need to be kept in mind, as troponin and NT-proBNP levels can be altered by renal insufficiency or by measures that influence heart failure independent of the state of AL disease. 23 NT-proBNP can also become elevated in patients treated with immunomodulatory agents independent of other laboratory values and may signal worsening heart failure. 40 While metrics for other organ responses are in use, they have not been validated to the degree that cardiac responses have been (Table 2).…”

“…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.…”

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

“…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.…”