A novel regimen combining high dose cytarabine and bortezomib has activity in multiply relapsed and refractory mantle cell lymphoma - long-term results of a multicenter observation study.
Salvage therapy for patients with mantle cell lymphoma (MCL) remains a challenge. The clinical course is characterised by increasing resistance to conventional chemotherapy and a dismal long-term outcome. On the basis of studies demonstrating synergy in vitro, eight heavily pretreated patients (median age 65 years) with advanced stage MCL were individually treated with a novel combination protocol consisting of the proteasome inhibitor bortezomib (1.5 mg/m(2); Days 1 and 4), high-dose cytarabine (750-2000 mg/m(2); Days 2 and 3) and dexamethasone (40 mg daily; Days 1-4). Rituximab (375 mg/m(2)) was added in patients not refractory to prior rituximab-containing regimens. Treatment was repeated in 3-week intervals or postponed until hematologic recovery for up to four planned cycles. Toxicity consisted mainly of Grade 3/4 hematotoxicity, which occurred in all patients. Median treatment interval was 31 days. Objective responses were observed in four (50%) of eight patients, including two complete remissions. Median progression free and overall survival were 5 and 15.5 months, respectively. The combination of bortezomib and a high-dose cytarabine-containing regimen has activity in heavily pretreated patients with relapsed or refractory MCL.
Department of Internal Medicine III, University of Munich, Munich, Germany. oliver.weigert@med.uni-muenchen.de
Oliver
O
Weigert
Eckhart
E
Weidmann
Rudolf
R
Mueck
Martin
M
Bentz
Christoph
C
von Schilling
Robert
R
Rohrberg
Kathleen
K
Jentsch-Ullrich
Wolfgang
W
Hiddemann
Martin
M
Dreyling
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003561:Cytarabine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis
D001897:Boronic Acids; D011719:Pyrazines; D003561:Cytarabine; D000069286:Bortezomib