Transient Post Chemotherapy Rise in NT Pro-BNP in AL Amyloidosis : Implications for Organ Response Assessment.

Abstract 1791

Poster Board I-817

N-terminal fragment of brain natriuretic peptide (NT Pro-BNP) is a cardiac biomarker that is used as a prognostic marker at diagnosis in AL amyloidosis and has been reported to change serially following treatment, in line with clonal responses. With our Italian colleagues, we recently reported that changes in NT Pro-BNP post chemotherapy have marked prognostic significance – patients who do not achieve a 30% decrease having worse outcomes. We now report a transient post chemotherapy rise in NT Pro-BNP as a new phenomenon and assess its significance, relating it to renal and cardiac function and to assess whether this phenomenon impacts on the rate of relapse or outcome.

Patients with systemic AL amyloidosis who received upfront treatment with either oral cyclophosphamide, thalidomide and dexamethasone (CTD) or oral melphalan-dexamethasone (Mel-Dex), with a creatinine clearance of >30 ml/min and who achieved a complete serum free light chain response were identified from the database of the UK National Amyloidosis Centre. NT pro-BNP levels alongside renal and cardiac function were analysed at the 0, 6 and 12 months after commencement of chemotherapy.

A total of 51 such patients identified. CTD was administered to 42 of these patients, Mel-Dex to the remaining 9 patients. A rise in NT Pro-BNP from baseline was seen in 36 (71%) patients at 6 months. The median NT pro-BNP increased from a baseline of 106pmol/L at 0 months to 194pmol/L at 6 months (median increase of 163pmol/L; p = 0.0001). A subsequent fall in their NT Pro-BNP levels was seen at 12 months in 33 (92%) of these patients to a median NT Pro-BNP value of 92pmol/L (median fall 157pmol/L; p = <0.0001). In 21 (64%) patients, the fall was to below diagnostic levels.

There was no significant rise in the creatinine at six months (p=0.439), suggesting that the rise in NT Pro-BNP was not due to a change in the renal function. None of the patients showed a significant change in the left ventricular wall thickness, systolic or diastolic function on echocardiography at 6 months. There was no difference in the rate of NT Pro-BNP rise when comparing the treatments received: 6/9 (67%) of Mel-Dex treated patients and 30/42 (71%) CTD treated patients experienced this NT Pro-BNP rise at six months. At a median follow-up of 29 months, there was no difference in the overall survival and the rate of clonal relapse was identical (44%) for patients who did and did not have an NT Pro-BNP rise at 6 months.

In conclusion, this series clearly shows that NT Pro-BNP values can rise transiently in the immediate post chemotherapy period in nearly three-quarters of patients with a complete FLC response. The exact mechanism for this is unclear. This rise is not associated with decline in cardiac function on echocardiography nor is it related to worsening renal function. It does not impact the rate of clonal relapse or overall survival. Given that fluid retention is a known side effect of thalidomide in amyloidosis, one could speculate that thalidomide could cause this transient rise in NT Pro-BNP. However, there was no difference in the percentage number of patients with a rise in NT Pro-BNP between the CTD and Mel-Dex groups (although numbers were very small in the latter group). Further data is needed for non-thalidomide based regimes to assess if this effect is seen to the same extent. This important but transient phenomenon can confound interpretation of treatment response. Immediate post treatment values should be reviewed carefully prior to being used for assessment of organ function or to be used as basis of treatment decisions.