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Dr. Kyle - Prognostic Value of the Serum Free Light Chain Ratio in Patients with Newly Diagnosed Myeloma: Proposed Incorporation into the International Staging System.
Robert A. Kyle, MD
Mayo Clinic
Rochester, Minnesota
Chairman, IMF Board of Scientific Advisors

"When we looked at the light chain that was most abnormal, this turned out to be an important prognostic feature in survival of patiens with multiple myeloma."
Dr. Robert Kyle

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[659] Prognostic Value of the Serum Free Light Chain Ratio in Patients with Newly Diagnosed Myeloma: Proposed Incorporation into the International Staging System. Session Type: Oral Session

Christine L.H. Snozek, Jerry A. Katzmann, Robert A. Kyle, Angela Dispenzieri, Dirk R. Larson, Raynell J. Clark, Philip R. Greipp, S. Vincent Rajkumar Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA; Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USA; Divisions of Biostatistics and Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, USA

Background: The serum free light chain (FLC) ratio is a readily available laboratory test that has independent prognostic significance in monoclonal gammopathy of undetermined significance (MGUS) (Blood 2005;106:812-17) and solitary plasmacytoma (Blood 2006;108:1979-83). The purpose of this study was to determine if the FLC ratio will be of prognostic value in multiple myeloma (MM). Methods: We used a well characterized cohort of 1027 newly diagnosed MM patients seen at Mayo Clinic from January 1, 1985 to December 31, 1998 (Mayo Clin Proc 2003;78:21-33) to ensure adequate follow up. Archived serum samples from blood drawn within 30 days of initial diagnosis were available on 790 of the 1027 patients. Quantitation of serum free and concentrations was performed on the archived sera by immunonephelometry, using specific antibodies on a BNII nephelometer. FLC ratio was calculated as /, i.e., free concentration divided by free , reference range 0.26-1.65. If the FLC ratio is >1.65, is considered to be the involved FLC and the uninvolved FLC, and vice versa if the ratio is less than 0.26. Incorporation of FLC into the International Staging System (ISS) was assessed in 576 of 790 patients (73%), in whom samples or data were available to estimate the ISS. Results: 790 patients (median age 66 years) were studied. The FLC ratio was outside the reference range in 95.1% of patients. The median involved and concentrations were 37.1 and 71.3 mg/dL, respectively. A cut-point / FLC ratio of <0.03 or >32 was chosen for further modeling analysis on the basis of its separation of the cohort into two roughly comparable parts. Overall survival was significantly inferior in patients with an FLC ratio <0.03 or >32 (n=479 patients) compared to those with an FLC ratio that was 0.03-32 (n=311 patients), with median survival of 30 versus 39 months, respectively, P<0.001 (hazard ratio 1.3, 95% CI 1.12-1.54). The FLC ratio (<0.03 or >32) retained independent significance after adjusting for the International Staging System (ISS) (P=0.03). The FLC ratio made the most significant contribution to predicting prognosis in patients with ISS Stage 2 (n=265 pts), separating this category of patients into those with 5 year survival rates of 20.5% (FLC ratio <0.03 or >32; n=152 pts) versus 35.2% (FLC ratio 0.03-32; n=113 pts), P=0.02. We studied the additional prognostic value of the serum FLC to the variables used in the ISS by defining FLC ratio <0.03 or >32, S2M 3.5 g/L, and serum albumin <3.5 g/dL as three risk factors in a risk-stratification model. Patients with 0, 1, 2, or 3 risk factors had significantly different overall survival, with median overall survival times of 51, 39, 30 and 22 months, respectively, P<0.001. Conclusions: The serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma. We show that the serum FLC ratio can be incorporated into the ISS, providing the greatest prognostic value in ISS Stage 2 patients, as well as providing a new risk-stratification model.

Abstract #659 appears in Blood, Volume 110, issue 11, November 16, 2007

Keywords: Risk Factor|Epitope Specific Antibody Assay|Clinical Outcome

Disclosure: Research Funding: This work was supported in part by research grants CA 107476 and CA 62242 from the National Cancer Institute.

Monday, December 10, 2007 4:30 PM

Session Info: Simultaneous Session: Multiple Myeloma: Biochemical and Genetic Prognosticators (3:30 p.m.-5:00 p.m.)

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