Abstract
To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma. 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. 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). 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.
Highlights
Experimental Design: To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma
Whereas early onset of CR after one or two induction chemotherapy cycles seems to be crucial to sustained remission in most systemic malignancies, the median time to CR in multiple myeloma is nearly 12 months, reaching a cumulative rate of f50% only at 3 years despite intensive treatment as Authors’Affiliations: 1Cancer Research and Biostatistics, Seattle,Washington and 2Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas Received 3/5/07; revised 5/9/07; accepted 5/24/07
Recent gene expression profiling GEP studies revealed that, in comparison with subjects with monoclonal gammopathy of undetermined significance (MGUS), patients with multiple myeloma and a MGUS-like signature enjoyed superior OS despite a significantly lower CR rate, compared with patients presenting with non-MGUS-like multiple myeloma [10]
Summary
Experimental Design: To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma. 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. 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. Data of CD138-purified plasma cells available for 326 patients [12], we examined the role of CR for OS and EFS in the context of low-risk and high-risk features defined according to SPF and GEP data [13]
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