TY - JOUR
T1 - Impact of high-risk classification by FISH
T2 - An Eastern Cooperative Oncology Group (ECOG) study E4A03
AU - Jacobus, Susanna J.
AU - Kumar, Shaji
AU - Uno, Hajime
AU - van Wier, Scott A.
AU - Ahmann, Greg J.
AU - Henderson, Kimberly J.
AU - Callander, Natalie S.
AU - Williams, Michael E.
AU - Siegel, David S.
AU - Greipp, Philip R.
AU - Rajkumar, S. Vincent
AU - Fonseca, Rafael
PY - 2011/11
Y1 - 2011/11
N2 - Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)-based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow-up approached 3years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P=0·004) corresponded to a hazard ratio of 3·48 [95% confidence interval: (1·42-8·53)], an effect also observed in multivariate analysis. Two-year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P=0·026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio=2·0 [0·7-5·6]), but overall response rates were not different. FISH-based risk classification retained prognostic significance in patients receiving lenalidomide-based induction.
AB - Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)-based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow-up approached 3years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P=0·004) corresponded to a hazard ratio of 3·48 [95% confidence interval: (1·42-8·53)], an effect also observed in multivariate analysis. Two-year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P=0·026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio=2·0 [0·7-5·6]), but overall response rates were not different. FISH-based risk classification retained prognostic significance in patients receiving lenalidomide-based induction.
KW - Bortezomib
KW - Dexamethasone
KW - FISH
KW - Lenalidomide
KW - Myeloma
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U2 - 10.1111/j.1365-2141.2011.08849.x
DO - 10.1111/j.1365-2141.2011.08849.x
M3 - Article
C2 - 21902684
AN - SCOPUS:80053965637
SN - 0007-1048
VL - 155
SP - 340
EP - 348
JO - British journal of haematology
JF - British journal of haematology
IS - 3
ER -