B-cell maturation antigen is expressed on plasma cells. In this study, we have identified serum B-cell maturation antigen as a novel biomarker that can monitor and predict outcomes for multiple myeloma patients. Compared to healthy donors, patients with multiple myeloma showed elevated serum B-cell maturation antigen levels (P<0.0001). Serum B-cell maturation antigen levels correlated with the proportion of plasma cells in bone marrow biopsies (Spearman’s rho = 0.710; P<0.001), clinical status (complete response vs. partial response, P=0.0374; complete response vs. progressive disease, P<0.0001), and tracked with changes in M-protein levels. Among patients with non-secretory disease, serum B-cell maturation antigen levels correlated with bone marrow plasma cell levels and findings from positron emission tomography scans. Kaplan-Meier analysis demonstrated that serum B-cell maturation antigen levels above the median levels were predictive of a shorter progression-free survival (P=0.0006) and overall survival (P=0.0108) among multiple myeloma patients (n=243). Specifically, patients with serum B-cell maturation antigen levels above the median level at the time of starting front-line (P=0.0043) or a new salvage therapy (P=0.0044) were found to have shorter progression-free survival. Importantly, serum B-cell maturation antigen levels did not show any dependence on renal function and maintained independent significance when tested against other known prognostic markers for multiple myeloma such as age, serum β2 microglobulin, hemoglobin, and bone disease. These data identify serum B-cell maturation antigen as a new biomarker to manage multiple myeloma patients.

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Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma.

New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.

Introduction: In addition to breast and colorectal cancers, multiple myeloma has also been associated with vitamin D deficiency. Given the role of vitamin D in calcium absorption and bone metabolism, it is crucial to maintain sufficient levels for multiple myeloma patients because of their high risk of bone-related complications. We hypothesized that there was a high prevalence of vitamin D deficiency and insufficiency among multiple myeloma patients. We also hypothesized that there is inadequate screening of vitamin D levels throughout community oncology clinics nationwide. Methods: This study both evaluated multiple myeloma patients from a single medical practice specializing in this B-cell malignancy who had a 25-OH vitamin D level determined, and separately determined the proportion of oncology sites that screen for this vitamin among their patients. Charts were reviewed from the medical practice specializing in multiple myeloma, and only the first vitamin D determination was analyzed in the study. Demographics and the presence of the following complications at the time or within 1 year from when vitamin D levels were assessed: peripheral neuropathy, skeletal-related events and bone disease. We defined skeletal-related events as pathological fractures, spinal cord compression or requirement for radiation or surgery, and bone disease as having one of the following: osteoporosis, osteopenia or lytic bone disease. Patients were categorized as either having sufficient (> 30 ng/ml), insufficient (20 to < 30 ng/ml) or deficient (<20 ng/ml) 25-OH vitamin D levels. Chi square analysis was used to compare the proportion of patients with specific complications to their 25-OH vitamin D levels. To determine the rate of vitamin D screening among community oncologists, Site Information Forms from 508 sites throughout the United States were reviewed which asked these groups whether they screen patients for vitamin D levels. Results: One hundred sixty-nine multiple myeloma patients were enrolled in the study. Their median age was 67, the mean was 65.4 (range, 38-85) and the gender breakdown was 62% male and 38% female. 25-OH vitamin D levels were sufficient in less than two-thirds (64%) of patients with 22% and 14% of patents showing insufficient and deficient levels of this vitamin, respectively. The proportions of patients with specific complications in relationship to their vitamin D levels are shown below.Abstract 5769. Table 1ComplicationVitamin D deficientVitamin D insufficientVitamin D deficientPeripheral neuropathy65%65%59%Bone disease85%82%87%Skeletal-related events70%62%58% Chi square analysis showed no significant differences in complications rates as related to vitamin D levels although skeletal-related events were more frequently observed among patients with vitamin D levels below the normal range (insufficient or deficient). Of the 508 sites that were asked on the Site Information Forms to provide information on whether their physicians assess vitamin D levels as part of their standard of care of their patients, 97% responded that they did not assess vitamin D levels as part of their standard of care of these patients. Conclusion: Vitamin D levels are frequently low among multiple myeloma patients and, despite this, screening levels of this vitamin is not thought to be part of the routine work up by the vast majority of oncologists in the United States. Disclosures No relevant conflicts of interest to declare.