Impact of high-risk classification by FISH: An Eastern Cooperative Oncology Group (ECOG) study E4A03

Susanna J. Jacobus, Shaji K Kumar, Hajime Uno, Scott A. van Wier, Greg J. Ahmann, Kimberly J. Henderson, Natalie S. Callander, Michael E. Williams, David S. Siegel, Philip R. Greipp, S Vincent Rajkumar, Rafael Fonseca

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalBritish Journal of Haematology
Volume155
Issue number3
DOIs
StatePublished - Nov 2011

    Fingerprint

Keywords

  • Bortezomib
  • Dexamethasone
  • FISH
  • Lenalidomide
  • Myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

Jacobus, S. J., Kumar, S. K., Uno, H., van Wier, S. A., Ahmann, G. J., Henderson, K. J., Callander, N. S., Williams, M. E., Siegel, D. S., Greipp, P. R., Rajkumar, S. V., & Fonseca, R. (2011). Impact of high-risk classification by FISH: An Eastern Cooperative Oncology Group (ECOG) study E4A03. British Journal of Haematology, 155(3), 340-348. https://doi.org/10.1111/j.1365-2141.2011.08849.x