TY - JOUR
T1 - Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling
AU - Haessler, Jeffrey
AU - Shaughnessy, John D.
AU - Zhan, Fenghuang
AU - Crowley, John
AU - Epstein, Joshua
AU - Van Rhee, Frits
AU - Anaissie, Elias
AU - Pineda-Roman, Mauricio
AU - Zangari, Maurizio
AU - Hollmig, Klaus
AU - Mohiuddin, Abid
AU - Alsayed, Yazan
AU - Hoering, Antje
AU - Tricot, Guido
AU - Barlogie, Bart
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-07-0527
DO - 10.1158/1078-0432.CCR-07-0527
M3 - Article
C2 - 18056185
AN - SCOPUS:37249040444
SN - 1078-0432
VL - 13
SP - 7073
EP - 7079
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -