Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis.

Patients with advanced cardiac AL amyloidosis have a poor prognosis. Early hematologic and cardiac responses can prolong survival, but predictors of these outcomes have yet to be clarified. We report on 142 patients with newly diagnosed stage IIIb AL amyloidosis according to the modified Mayo 2004 and Boston University staging systems. After a median follow-up of 60 months, the median overall survival (OS) was 9 months. Independent baseline factors associated with shorter OS were symptom onset to diagnosis >6 months (HR 1.94, p=0.003); bone marrow plasmacytosis 10% (HR 1.98; p=0.01); troponin I >0.635 ng/mL (HR 1.62; p=0.04); New York Heart Association class III/IV (HR 1.67; p=0.04); and 6-minute walk test distance <200 meters (HR 1.85; p=0.01). Early hematologic (within 1 month) and cardiac (within 3 months) responses were significantly associated with longer survival. In a one-month landmark analysis, patients with a hematologic very good partial response, partial response, and no response had a median OS of 47, 25, and 5 months, respectively (p<0.0001). Patients with cardiac response at 3 months had significantly longer OS (47 vs. 11 months; p<0.0001). On multivariable modeling, bortezomib use was associated with early hematologic (OR 4.54; p=0.03) and cardiac (OR 5.11; p=0.04) responses and longer OS (HR 0.43; p<0.001). Symptom onset to diagnosis duration of >6 months (OR 0.27; p=0.01) and dFLC >350 mg/L (OR 0.21; p=0.03) were independently associated with lower odds of an early cardiac response. This study identified factors predictive of treatment outcomes and prognostic for survival in advanced cardiac AL amyloidosis.