Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial.
High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving < or =2 organ systems were assigned to MEL 100, 140, or 200 mg/m(2) with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients.
Cohen
Adam D
AD
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. cohena@mskcc.org
Zhou
Ping
P
Chou
Joanne
J
Teruya-Feldstein
Julie
J
Reich
Lilian
L
Hassoun
Hani
H
Levine
Beth
B
Filippa
Daniel A
DA
Riedel
Elyn
E
Kewalramani
Tarun
T
Stubblefield
Michael D
MD
Fleisher
Martin
M
Nimer
Stephen
S
Comenzo
Raymond L
RL
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007147:Immunoglobulin Light Chains; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012074:Remission Induction; D018570:Risk Assessment; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*; D014182:Transplantation, Autologous
D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D007147:Immunoglobulin Light Chains; D019653:Myeloablative Agonists; D013792:Thalidomide; D003907:Dexamethasone; D008558:Melphalan