Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling.
METHODS
To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma.


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.
Haessler
Jeffrey
J
Cancer Research and Biostatistics, Seattle, Washington, USA.
Shaughnessy
John D
JD
Zhan
Fenghuang
F
Crowley
John
J
Epstein
Joshua
J
van Rhee
Frits
F
Anaissie
Elias
E
Pineda-Roman
Mauricio
M
Zangari
Maurizio
M
Hollmig
Klaus
K
Mohiuddin
Abid
A
Alsayed
Yazan
Y
Hoering
Antje
A
Tricot
Guido
G
Barlogie
Bart
B
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D009101:Multiple Myeloma / Q000097:blood / Q000235:genetics* / Q000601:surgery*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D013792:Thalidomide