Summary Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age‐matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.

Immunosuppressed patients are known to have an increased incidence of skin cancer. Patients with multiple myeloma (MM) show impaired immune function. In the past, because of poor survival, the incidence of specific secondary primary malignancies such as skin cancer among these patients was difficult to establish. With more effective MM therapies that have emerged in recent years, these patients are living markedly longer, and therefore, it becomes of increasing importance to determine whether their risk of developing other medical problems such as skin cancer is increased. We performed a retrospective cohort study of 205 myeloma patients and 193 age-, race-, and gender-matched control subjects to assess the incidence of skin cancers among patients with MM and determine the specific types of and risk factors for skin cancer. We found that there is an increased occurrence of skin cancer among patients with MM compared to control subjects (26.8% vs. 16.1% in controls; P = 0.009). Among specific types of skin cancer, the proportion of patients with squamous cell carcinoma (SCC) was higher than controls (P = 0.016). In addition to MM diagnosis, older age and Caucasian ethnicity were predictors of skin cancer of any type. Furthermore, older age was also a predictor of SCC.

e20044 Background: Multiple myeloma (MM) patients (pts) have shown a higher risk of developing other cancers, although the type, time course, and relationship to MM treatment of these cancers are less clear. In this study, we determined the risk of specific skin cancer (CA) types among MM patients and its relationship to onset of MM and treatment. Methods: MM pts and unrelated age, sex, and race-matched companions (controls) seen at a MM clinic were enrolled in a retrospective cohort study. Information regarding baseline characteristics of MM and history of skin CA was obtained from medical records. Overall skin CA prevalence and types were compared between groups; among MM patients, the occurrence of skin CA was analyzed relative to date of diagnosis and treatment regimens, with stratification according to treatment duration. Results: We enrolled 205 MM pts and 201 controls with 27.3% and 14.9% demonstrating skin CA, respectively (p < 0.001). Specific types of skin CA included 60 and 37 basal cell carcinomas (BCC), 50 and 17 squamous cell carcinomas (SCC), and 9 and 5 melanomas in the MM pts and controls, respectively. The standardized incidence ratios (SIR) were SCC: 2.88 (p< 0.001), BCC: 1.59 (p<0.001), and melanoma: 1.76 (p = 0.074). SCC SIR was elevated (p<0.001) across each yearly time point from 10 years prior to MM diagnosis through 10 years subsequent to MM diagnosis. BCC SIR was elevated (p <0.002) from 7 through 10 years following MM diagnosis. The SIR markedly increased over time following the diagnosis of MM for both SCC and BCC. Relative risk (RR) was determined for pts treated with bortezomib, immunomodulatory agents, alkylating agents, glucocorticoids, and anthracyclines. There was no significant increase in RR overall or for any specific type of skin CA in relationship to the type or duration of MM treatment. Conclusions: MM pts show an increased risk of skin CA (there was no increase in melanoma incidence), including SCC and BCC. SCC occurred before and following the diagnosis of MM whereas BCC followed the diagnosis of MM. The post-MM diagnosis increase in skin CA was not related to specific drugs used to treat MM.

4026 Background: B cell maturation antigen (BCMA) is a receptor whose expression increases during B-cell development and is found on malignant cells from multiple myeloma (MM) patients; however, it has not been identified in human serum. Methods: Following informed consent (Western IRB BIO 001), serum was isolated from MM patients and analyzed with a BCMA enzyme-linked immunosorbent assay. Values represent the mean of triplicate experiments. Our human MM xenograft (LAGκ-2) was grown in SCID mice, and animals were treated with bortezomib (BORT) and cyclophosphamide (CY); tumor volume and BCMA levels were determined. Statistical significance of differences observed was determined using a Student's t test and analysis was determined using GraphPad prism software. Results: The serum BCMA levels from newly diagnosed MM patients (n = 58) was much higher (13.26 ng/ml) than among age-matched healthy subjects (n = 45; median 2.57 ng/ml; P < 0.0001) and MGUS subjects (n = 25; median 4.43 ng/ml; P = 0.002). Notably, protein levels were much higher among patients with relapsed or refractory disease (n = 88; median 18.99 ng/ml) compared to those with responsive (> partial response) disease (n = 95; median 3.48 ng/ml; P = 0.0016). Following treatment, patients with responsive disease showed decreases in BCMA levels whereas those with progressive disease showed increases. Additionally, with a median follow-up of 8 months (range, < 0 – 83 months), MM patients (n = 193) with BCMA levels above the median (8.43 ng/ml) showed a shortened survival compared to those with amounts below the median concentration (P < 0.0001). Following treatment with BORT and CY, we also showed a marked decrease in tumor volume and serum human BCMA levels in mice bearing the MM LAGκ-2 xenograft whereas untreated animals showed marked increases in tumor size and serum BCMA. Conclusions: This is the first report identifying serum BCMA in any human disease and suggests that these levels may be a novel biomarker for monitoring disease status and therapeutic response in MM patients. Disclosures: No relevant conflicts of interest to declare.

e18549 Background: B cell maturation antigen (BCMA) is a receptor whose expression increases during B-cell development and is found on malignant cells from multiple myeloma (MM) patients; however, it has not been identified in human serum. Methods: Bone marrow (BM) aspirates and peripheral blood were obtained from patients with MM, monoclonal gammopathy of undetermined significance (MGUS) and healthy control subjects following informed consent (Western IRB BIO 001). Serum was isolated and analyzed with a BCMA enzyme‑linked immunosorbent assay. Values represent the mean of triplicate experiments. BM mononuclear cells (MCs) were isolated using density‑gradient centrifugation and cultured for 72 h in RPMI1640 supplemented with 10% fetal bovine serum. Our human MM xenograft (LAGκ-2)was grown in SCID mice and treated with bortezomib (BORT) with cyclophosphamide (CY); tumor volume and BCMA levels were determined. Statistical significance of differences observed was determined using a Student’s t test and analysis was determined using GraphPad prism software. Results: We showed that the supernatants of cultured BMMCs from MM patients had high concentrations of BCMA (median = 2,250 pg/ml) whereas normal subjects showed minimal amounts (56 ng/ml; P < 0.0001). The serum BCMA levels from newly diagnosed MM patients (n = 51) had much higher levels (13.74 ng/ml) than among controls (n = 40; median 2.58 ng/ml; P < 0.0001) and MGUS subjects (n = 26; median 5.40 ng/ml; P = 0.005). Notably, protein levels were much higher among patients with relapsed or refractory (R/R) disease (n = 79; median 20.02 ng/ml) compared to those with responsive (> partial response) disease (n = 80; median 4.14 ng/ml; P = 0.0038). Following treatment, patients with responsive disease showed decreases in BCMA levels whereas those with R/R disease showed increases. Following treatment with BORT and CY, we also showed a marked decrease in tumor volume and serum human BCMA levels in mice bearing the LAGκ-2 xenograft whereas untreated animals showed marked increases in tumor size and serum BCMA. Conclusions: This is the first report identifying serum BCMA in any human disease and suggests that these levels may be a novel biomarker for monitoring disease status and therapeutic response of MM patients.