The clinical significance of molecular response in indolent follicular lymphomas.
Most patients with follicular lymphoma (FL) achieve a complete response (CR) after treatment, but eventually most of them, particularly those with stage IV, relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a rearrangement of the bcl-2 oncogene that constitutes an excellent target for detection of MRD by polymerase chain reaction (PCR). One hundred ninety-four previously untreated patients with indolent FL and detectable bcl-2 rearrangement were studied. The PCR assay was used to detect bcl-2-rearranged cells in blood and marrow before and after treatment. Molecular response rate was 37%, 53%, 56%, and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of therapy, respectively. Although molecular response was higher among clinical CRs, one third of partial responders at 3 to 5 months also achieved a molecular response. Patients who achieved a molecular response during the first year of treatment had a significantly longer failure-free survival (FFS) than those who did not (4-year FFS: 76% v 38%, respectively; P < .001). Similar results were also observed in the subset of patients in clinical CR 1 year after treatment. By multivariate analysis, beta2-microglobulin (beta2-M; P < .01), and molecular response (P < .001) were the most important variables associated with outcome. When we combined beta2-M and molecular response, three prognostic groups emerged: (1) low beta2-M and molecular responders, (2) low beta2-M and nonresponders or high beta2-M and responders, and (3) high beta2-M and nonresponders. The 4-year FFS of these 3 groups were 86%, 65%, and 23%, respectively. Finally, patients who achieved molecular response and sustained it had better FFS than those who either reverted back to PCR-positive or who never achieved molecular response. Serial PCR analysis to determine the molecular response in FL correlates well with outcome especially when combined with pretreatment beta2-M.
López-Guillermo
A
A
Department of Lymphoma, Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
Cabanillas
F
F
McLaughlin
P
P
Smith
T
T
Hagemeister
F
F
Rodríguez
M A
MA
Romaguera
J E
JE
Younes
A
A
Sarris
A H
AH
Preti
H A
HA
Pugh
W
W
Lee
M S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012008:Recurrence; D016019:Survival Analysis
D019253:Proto-Oncogene Proteins c-bcl-2