Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma.
OBJECTIVE
We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission.


METHODS
Patients with CD20(+) stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment.


RESULTS
A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. (90)Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After (90)Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients.


CONCLUSIONS
Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.
Morschhauser
Franck
F
Centre Hospitalier Universitaire, Lille, France.
Radford
John
J
Van Hoof
Achiel
A
Vitolo
Umberto
U
Soubeyran
Pierre
P
Tilly
Herve
H
Huijgens
Peter C
PC
Kolstad
Arne
A
d'Amore
Francesco
F
Gonzalez Diaz
Marcos
M
Petrini
Mario
M
Sebban
Catherine
C
Zinzani
Pier Luigi
PL
van Oers
Marinus H J
MH
van Putten
Wim
W
Bischof-Delaloye
Angelika
A
Rohatiner
Ama
A
Salles
Gilles
G
Kuhlmann
Jens
J
Hagenbeek
Anton
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002170:Canada; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016499:Radioimmunotherapy; D018714:Radiotherapy, Adjuvant; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab; C422802:ibritumomab tiuxetan