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.
RCT Entities:
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.
Authors: V Arzoumanian; A Hoering; J Sawyer; F van Rhee; C Bailey; J Gurley; J D Shaughnessy; E Anaissie; J Crowley; B Barlogie Journal: Leukemia Date: 2008-01-17 Impact factor: 11.528
Authors: Sathish Gopalakrishnan; Anita D'Souza; Emma Scott; Raphael Fraser; Omar Davila; Nina Shah; Robert Peter Gale; Rammurti Kamble; Miguel Angel Diaz; Hillard M Lazarus; Bipin N Savani; Gerhard C Hildebrandt; Melhem Solh; Cesar O Freytes; Cindy Lee; Robert A Kyle; Saad Z Usmani; Siddhartha Ganguly; Amer Assal; Jesus Berdeja; Abraham S Kanate; Binod Dhakal; Kenneth Meehan; Tamila Kindwall-Keller; Ayman Saad; Frederick Locke; Sachiko Seo; Taiga Nishihori; Usama Gergis; Cristina Gasparetto; Tomer Mark; Yago Nieto; Shaji Kumar; Parameswaran Hari Journal: Biol Blood Marrow Transplant Date: 2018-12-21 Impact factor: 5.742
Authors: Shaji K Kumar; Joseph R Mikhael; Francis K Buadi; David Dingli; Angela Dispenzieri; Rafael Fonseca; Morie A Gertz; Philip R Greipp; Suzanne R Hayman; Robert A Kyle; Martha Q Lacy; John A Lust; Craig B Reeder; Vivek Roy; Stephen J Russell; Kristen E Detweiler Short; A Keith Stewart; Thomas E Witzig; Steven R Zeldenrust; Robert J Dalton; S Vincent Rajkumar; P Leif Bergsagel Journal: Mayo Clin Proc Date: 2009-12 Impact factor: 7.616
Authors: Antje Hoering; John Crowley; John D Shaughnessy; Klaus Hollmig; Yazan Alsayed; Jackie Szymonifka; Sarah Waheed; Bijay Nair; Frits van Rhee; Elias Anaissie; Bart Barlogie Journal: Blood Date: 2009-06-10 Impact factor: 22.113
Authors: Twyla B Bartel; Jeff Haessler; Tracy L Y Brown; John D Shaughnessy; Frits van Rhee; Elias Anaissie; Terri Alpe; Edgardo Angtuaco; Ronald Walker; Joshua Epstein; John Crowley; Bart Barlogie Journal: Blood Date: 2009-05-14 Impact factor: 22.113