Abstract
Abstract 1756
We hypothesized that surrogate markers of host immune response to clonal myeloproliferation predict survival in myeloid malignancies. Because of immediate applicability to current practice, we chose plasma immunoglobulin free light chain (FLC) concentration (B-cell activation marker) as the biomarker of interest.
Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Both groups were fully annotated for karyotype. Kappa (κ) and lambda (λ) FLC were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded.
Above upper normal-limit values for κ or λ FLC was documented in 33% of 240 study patients with PMF and 46% of 74 patients with MDS. Multivariable analysis revealed significant associations between increased FLC and elevated creatinine, as well as advanced age in PMF (p=0.0004) and hemoglobin <10 g/dL in MDS (p=0.005). Increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Receiver-operating characteristic analysis-based cutoff levels for κ plus λ total FLC delineated risk groups with highly significant differences in overall survival (Figure); International Prognostic Scoring System-adjusted HR (95% CI) in PMF was 1.9 (1.3-2.7) and in MDS 6.3 (2.7-16.6). No correlations were seen with leukemia-free survival, karyotype or JAK2, MPL or IDH mutations.
Elevated plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biological phenomenon that might be applicable to other malignant and non-malignant conditions.
Overall survival of primary myelofibrosis (PMF) patients stratified by plasma free light chain (FLC) concentration above or below the receiver operating characteristic (ROC) analysis-derived cutoff (3.78 g/dL) (p<0.0001).
Overall survival of primary myelofibrosis (PMF) patients stratified by plasma free light chain (FLC) concentration above or below the receiver operating characteristic (ROC) analysis-derived cutoff (3.78 g/dL) (p<0.0001).
Overall survival of de novo myelodysplastic syndrome (MDS) patients stratified by plasma free light chain (FLC) concentration above or below the receiver operating characteristic (ROC) analysis-derived cutoff (3.24 g/dL) (p<0.0001).
Overall survival of de novo myelodysplastic syndrome (MDS) patients stratified by plasma free light chain (FLC) concentration above or below the receiver operating characteristic (ROC) analysis-derived cutoff (3.24 g/dL) (p<0.0001).
No relevant conflicts of interest to declare.
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