Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling

Jeffrey Haessler, John D. Shaughnessy, Fenghuang Zhan, John Crowley, Joshua Epstein, Frits Van Rhee, Elias Anaissie, Mauricio Pineda-Roman, Maurizio Zangari, Klaus Hollmig, Abid Mohiuddin, Yazan Alsayed, Antje Hoering, Guido Tricot, Bart Barlogie

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80 Scopus citations

Abstract

Experimental Design: To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma. Patients and Methods: Newly diagnosed patients with myeloma received a tandem autotransplant regimen. Using multivariate regression analyses, we examined the prognostic implications of time-dependent onset of CR on overall survival and event-free survival in the context of standard prognostic factors (SPF) and gene expression profiling - derived data available for 326 patients. Results: CR benefited patients regardless of risk status when only SPFs were examined. With knowledge of gene array data, a survival (and event-free survival) benefit of CR only pertained to the small high-risk subgroup of 13% of patients (hazard ratio, 0.23; P = 0.001), whereas the majority of patients with low-risk disease had similar survival expectations whether or not CR was achieved (hazard ratio, 0.68; P = 0.128). Conclusions: Access to gene expression information permitted the recognition of a small very high-risk subgroup of 13% of patients, in whom prolonged survival critically depended on achieving CR. Absence of such benefit in the remainder should lead to a reassessment of clinical trial designs that rely on this end point as a surrogate for long-term prognosis.

Original languageEnglish (US)
Pages (from-to)7073-7079
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number23
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Haessler, J., Shaughnessy, J. D., Zhan, F., Crowley, J., Epstein, J., Van Rhee, F., Anaissie, E., Pineda-Roman, M., Zangari, M., Hollmig, K., Mohiuddin, A., Alsayed, Y., Hoering, A., Tricot, G., & Barlogie, B. (2007). Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling. Clinical Cancer Research, 13(23), 7073-7079. https://doi.org/10.1158/1078-0432.CCR-07-0527