Bortezomib after dose-reduced allogeneic stem cell transplantation for multiple myeloma to enhance or maintain remission status.
OBJECTIVE
We investigated the effect of at least two cycles of bortezomib (1.3 mg/m(2) intravenously, days 1, 4, 8, and 11) after dose-reduced allogeneic stem cell transplantation (SCT) on toxicity, CD3(+) cells, graft-versus-host disease (GvHD), and response in patients with multiple myeloma.


METHODS
Eighteen patients with multiple myeloma without progressive disease were included. The proteasome inhibitor was given at median of 8 months after allografting to enhance or maintain remission status.


RESULTS
Fourteen patients (78%) completed the proposed two cycles. Four patients had to discontinue therapy due to neurotoxicity (n = 3) or gastrointestinal toxicity (n = 1). Severe grade III/IV toxicity was seen for thrombocytopenia (50%), leukopenia (17%), or neuropathy (17%), which was more often seen in patients treated concomitantly with cyclosporine (p = 0.06). The median circulating CD3(+) cells decreased during treatment from 550 muL to 438 muL (p = 0.03), resulting in herpes zoster infection in three patients (17%). In three patients, a mild aggravation of existing acute or chronic GvHD of the skin, and in one patient de novo skin grade I acute GvHD was noted. In patients with measurable disease, complete remission, partial remission, and minor response was seen in 3 (30%), 5 (50%), and 2 (20%) patients, respective.


CONCLUSIONS
Bortezomib after allogeneic SCT is effective but further studies are needed to balance the efficacy with potential hazards such as infectious complications, aggravation of GvHD, and neurotoxicity.
Kröger
Nicolaus
N
Department of Bone Marrow Transplantation, Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Zabelina
Tatjana
T
Ayuk
Francis
F
Atanackovic
Djordje
D
Schieder
Heike
H
Renges
Helmut
H
Zander
Axel
A
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D017252:CD3 Complex / Q000097:blood; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology; D006562:Herpes Zoster / Q000209:etiology; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications / Q000628:therapy*; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D033581:Stem Cell Transplantation; D013921:Thrombocytopenia / Q000139:chemically induced; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D001897:Boronic Acids; D017252:CD3 Complex; D011719:Pyrazines; D000069286:Bortezomib; D016572:Cyclosporine