TY - JOUR
T1 - Impact of Induction Therapy on the Outcome of Immunoglobulin Light Chain Amyloidosis after Autologous Hematopoietic Stem Cell Transplantation
AU - Afrough, Aimaz
AU - Saliba, Rima M.
AU - Hamdi, Amir
AU - Honhar, Medhavi
AU - Varma, Ankur
AU - Cornelison, A. Megan
AU - Rondon, Gabriela
AU - Parmar, Simrit
AU - Shah, Nina D.
AU - Bashir, Qaiser
AU - Hosing, Chitra
AU - Popat, Uday
AU - Weber, Donna M.
AU - Thomas, Sheeba
AU - Orlowski, Robert Z.
AU - Champlin, Richard E.
AU - Qazilbash, Muzaffar H.
N1 - Publisher Copyright:
© 2018
PY - 2018/11
Y1 - 2018/11
N2 - With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. 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: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P =.001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P =.3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P =.02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P =.07; hazard ratio,.5; 95% confidence interval [CI],.3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P =.05; hazard ratio,.4; 95% CI,.2 to.9). On multivariate analysis a low β2-microglobulin (P =.01; hazard ratio,.3; 95% CI,.1 to.7) and induction therapy with IMiD/PI (P =.01; hazard ratio,.3; 95% CI,.1 to.7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT.
AB - With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. 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: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P =.001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P =.3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P =.02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P =.07; hazard ratio,.5; 95% confidence interval [CI],.3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P =.05; hazard ratio,.4; 95% CI,.2 to.9). On multivariate analysis a low β2-microglobulin (P =.01; hazard ratio,.3; 95% CI,.1 to.7) and induction therapy with IMiD/PI (P =.01; hazard ratio,.3; 95% CI,.1 to.7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT.
KW - AL amyloidosis
KW - Autologous hematopoietic stem cell transplantation
KW - Induction therapy
KW - Response
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85052739618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052739618&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2018.07.010
DO - 10.1016/j.bbmt.2018.07.010
M3 - Article
C2 - 30016656
AN - SCOPUS:85052739618
SN - 1083-8791
VL - 24
SP - 2197
EP - 2203
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -