Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.
OBJECTIVE
Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL.


METHODS
Patients received either a single intravenous (IV) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel.


RESULTS
ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56% for the rituximab group (P =.002). Complete response (CR) rates were 30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group (P =.6), and time to progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable responses of > or = 6 months were 64% versus 47% (P =.030). Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan.


CONCLUSIONS
Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.
Witzig
Thomas E
TE
Division of Internal Medicine and Hematology, Nuclear Medicine, Mayo Clinic and Mayo Foundation, 60 Stabile Building, Rochester, MN 55905, USA. witzig@mayo.edu
Gordon
Leo I
LI
Cabanillas
Fernando
F
Czuczman
Myron S
MS
Emmanouilides
Christos
C
Joyce
Robin
R
Pohlman
Brad L
BL
Bartlett
Nancy L
NL
Wiseman
Gregory A
GA
Padre
Norman
N
Grillo-López
Antonio J
AJ
Multani
Pratik
P
White
Christine A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D011877:Radionuclide Imaging; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan