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Impact of Induction Therapy on the Outcome of Immunoglobulin Light Chain Amyloidosis after Autologous Hematopoietic Stem Cell Transplantation
Afrough, A., Saliba, R. M., Hamdi, A., Honhar, M., Varma, A., Cornelison, A. M., Rondon, G., Parmar, S., Shah, N. D., Bashir, Q., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
BACKGROUND With the availability of immunomodulatory agents (IMiD) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy prior to autologous hematopoietic stem cell transplant (auto-HCT). In this study, we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. METHODS We identified 128 patients with AL who underwent high-dose chemotherapy and auto- HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: 1) no induction 2) conventional chemotherapy (CC) - based induction (melphalan, steroids), and 3) IMiD/PI- based induction (thalidomide, lenalidomide or bortezomib). The hematologic (HR) and organ responses were defined according to the established criteria. RESULTS Median age at auto-HCT was 58 years (range, 35 - 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC and 83 (65%) received IMiD/PI. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), 18 (14%) patients, respectively. Post auto-HCT, 12 of 20 (60%), 15 of 24 (62%) and 72 of 83 (87%) evaluable patients achieved HR at 100-day in no induction, CC and IMiD/PI groups, respectively (p=0.001). Organ response at 1-year post auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%) and 37 of 79 (47%) evaluable patients in no induction, CC and IMiD/PI groups, respectively, (P=0.3). Achieving a hematologic CR was associated with a significantly higher probability of achieving an organ response (p=0.02). After a median follow up of 26 months, 2-year progression-free survival were 67%, 56% and 73% in no induction, CC and IMiD/PI groups, respectively (p=0.07, HR 0.5, 95% CI 0.3-1.1). 2-year overall survival (OS) was 73%, 76%, and 87% in no induction, CC and IMiD/PI, respectively (p=0.05, HR 0.4, 95% CI 0.2-0.9). On multivariate analysis, a low beta 2 microglobulin (p=0.01, HR 0.3, 95% CI 01-0.7) and induction therapy with IMiD/PI (p=0.01, HR 0.3, 95% CI 0.1-0.7) were associated with a better OS. CONCLUSIONS Induction therapy with either CC or IMiD/PI is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer OS compared to patients who received no induction or conventional chemotherapy before auto-HCT.