Outcomes for patients with systemic light chain amyloidosis and Mayo stage 3B disease.

Abstract

Patients with cardiac light chain amyloidosis and Mayo stage 3b disease define a high-risk population with very poor prognosis. Here, we report treatment outcomes of 80 consecutive patients with newly diagnosed AL and Mayo 3b who received novel regimens. Early mortality (<1month) rate was 12.5%. On intention-to-treat, overall hematologic response rate was 40%, with complete response (CR)/very good partial response (VGPR) in 25% and partial response (PR) in 15%. At 1- and 3- month landmark analysis CR or VGPR/PR rates were 25%/23.5% and 34%/25.5%, respectively. Among patients that were treated with daratumumab-based therapies, 52.6% and 85.7% achieved at least VGPR within one 1 and 3months, respectively. Three-month cardiac response rate was 11.3% and 6-month was 18.8%. At least hemVGPR at 3months was associated with cardiac response at 6months (p=0.034). Median overall survival (OS) was 6.3months. At 1-month landmark at least hemPR was associated with better median OS (24.1 vs. 4.9months, p=0.017) and at 3-month landmark, at least hemVGPR was associated with a median OS of 40.7 versus 17months for hemPR and 7.4months for those without hematologic response (p=0.028). Cardiac response at 3months was associated with longer median OS (59.7 vs. 10.9months, p=0.044). Factors associated with poorer survival were κ-light chain amyloidosis (median OS 2.9 vs. 7.4months, p=0.028), peripheral nerve involvement (3.4 vs. 10.45months, p=0.024), systolic blood pressure <90mmHg (2 vs. 8months, p=0.002), baseline LVEF <55% (median OS 3.4 vs. 32months, p=0.29) and New York Heart Association (NYHA) class (2.7months for NYHA 3B-4 vs. 8months for NYHA 2-3A, p=0.02). Twenty-one patients (26.3%) received salvage therapy and ORR was 57.1%. Median OS for patients who received second line therapy was 24months. In conclusion, patients with Mayo 3b disease benefit from early hematologic response but cardiac response rates remain low.