Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study.
Forty patients were enrolled in this phase 2 study combining radioimmunotherapy (RIT) using yttrium-90-ibritumomab-tiuxetan (15 MBq [0.4 mCi]/kg) with reduced-intensity conditioning (RIC) using fludarabine (90 mg/m(2)) and 2 Gy total body irradiation followed by allogeneic hematopoietic cell transplantation (HCT) from related (n = 13) or unrelated (n = 27) donors for the treatment of advanced non-Hodgkin lymphoma. Diagnoses were follicular lymphoma (n = 17), chronic lymphocytic leukemia (n = 13), mantle cell lymphoma (n = 8), marginal zone lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1). Median age was 55 years (range, 34-68 years). All patients were high risk with refractory disease or relapse after preceding autologous HCT. No additional toxicities attributable to RIT were observed. Engraftment was rapid and sustained. Incidences of acute graft-versus-host disease 2-4 and chronic graft-versus-host disease were 43% and 53%, respectively. Kaplan-Meier-estimated nonrelapse mortality was 45% at 2 years. Twenty-two of 40 patients (55%) are alive, resulting in a Kaplan-Meier-estimated 2-year survival of 51% for all, 67% for follicular lymphoma, 49% for chronic lymphocytic leukemia, and 37% for mantle cell lymphoma patients. The combined use of RIT with RIC is feasible with acceptable toxicity, even in elderly and heavily pretreated patients. This study is registered at www.clinicaltrials.gov as #NCT00302757.
Bethge
Wolfgang A
WA
Medical Center, Department of Hematology & Oncology, University of Tuebingen, Tuebingen, Germany. wolfgang.bethge@med.uni-tuebingen.de
Lange
Thoralf
T
Meisner
Christoph
C
von Harsdorf
Stephanie
S
Bornhaeuser
Martin
M
Federmann
Birgit
B
Stadler
Michael
M
Uharek
Lutz
L
Stelljes
Matthias
M
Knop
Stefan
S
Wulf
Gerald
G
Trenschel
Rudolf
R
Vucinic
Vladan
V
Dittmann
Helmut
H
Faul
Christoph
C
Vogel
Wichard
W
Kanz
Lothar
L
Bunjes
Donald
D
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006402:Hematologic Diseases / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000737:chemistry / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan