Quantitative PCR analysis for Bcl-2/IgH in a phase III study of Yttrium-90 Ibritumomab Tiuxetan as consolidation of first remission in patients with follicular lymphoma.
PURPOSE The randomized First-Line Indolent Trial (FIT) was conducted in patients with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of yttrium-90 ((90)Y) ibritumomab tiuxetan given as consolidation of complete or partial remission. This study of minimal residual disease was undertaken in parallel, to determine the rate of conversion from bcl-2 polymerase chain reaction (PCR) -detectable to -undetectable status and the corresponding effect on progression-free survival (PFS). PATIENTS AND METHODS Blood samples from 414 patients ((90)Y-ibritumomab, n = 208; control, n = 206) were evaluated using real-time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis. Results Overall, 90% of treated patients converted from bcl-2 PCR-detectable to -undetectable disease status, compared with 36% in the control group. Treatment significantly prolonged median PFS in patients converting to bcl-2 PCR-undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in the control group; P < .01, HR, 0.293). CONCLUSION Eradication of PCR-detectable disease occurred more frequently after treatment with (90)Y-ibritumomab tiuxetan and was associated with prolongation of PFS.
Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, 45 Little Britain, London EC1A 7BE, United Kingdom.
Lindsey
L
Goff
Karin
K
Summers
Sameena
S
Iqbal
Jens
J
Kuhlmann
Michael
M
Kunz
Tom
T
Louton
Anton
A
Hagenbeek
Franck
F
Morschhauser
Barbara
B
Putz
Andrew
A
Lister
Ama
A
Rohatiner
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D023061:Gene Order; D019254:Genes, bcl-2; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan