Abstract P1-02-10: Reduced serum B-cell maturation antigen levels predict poor outcome in metastatic breast cancer patients in a phase 3 randomized 2nd-line hormone therapy trial

Abstract

Background: B-cell maturation antigen (BCMA) is a member of the tumor necrosis factor receptor family and has two ligands, B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL). These ligands activate cell proliferation and inhibit apoptosis of normal and malignant B-cells including in multiple myeloma (MM) cell lines. Berenson et al have recently reported that circulating BCMA levels are elevated in B-cell malignancies and can be used to monitor disease and predict PFS and OS for patients with MM, Waldenstroms's macroglobulinemia and chronic lymphocytic leukemia (CLL). On the other hand, recent studies have shown that serum BCMA levels are very low among patients with MM in complete remission with low antibody levels and those with primary immune deficiencies specifically those with combined variable immune deficiency and X-linked agammaglobulinemia. Studies of the potential role of serum BCMA for patients with solid tumors has not been evaluated to date. Methods: The pretreatment serum from 139 patients with hormone receptor-positive metastatic breast cancer who were enrolled in a phase 3 randomized clinical trial of second-line hormone therapy was evaluated using an ELISA for BCMA. The BCMA ELISA was from R&D Systems (Minneapolis, MN). Serum BCMA was correlated with TTP using categorical serum BCMA cutpoints. Results: Pretreatment serum BCMA levels had a median of 55.61 ng/ml, an interquartile range of 34.20 and 78.79 ng/ml, and full range from 3.99 to 1193.26 ng/ml. In univariate analysis for TTP, reduced serum BCMA correlated with shorter TTP at the following dichotomous cutpoints: 15 ng/ml [HR=2.60, p=0.064, n=6 (4.3%) of patients below cutpoint]; 20 ng/ml [HR=2.88, p=0.005, n=10 (7.2%) of patients below cutpoint]; 25 ng/ml [HR=2.16, p=0.023, n=13 (9.4%) of patients below cutpoint]; and 30 ng/ml [HR=1.77, p=0.016, n=27 (19.4%) of patients below the cutpoint]. Conclusions: In a phase 3 randomized clinical trial of second-line hormone therapy among patients with hormone receptor-positive metastatic breast cancer, reduced pretreatment serum BCMA was associated with shorter TTP. This may be due to the association of reduced serum BCMA with immune deficiency; and, thus, lead to shorter TTP among patients with metastatic breast cancer. Evaluation of serum BCMA as a new biomarker to predict outcomes for breast cancer and other solid tumor patients deserves further study. Citation Format: Ali SM, Leitzel K, Li M, Udd K, Wang J, Sanchez E, Chen H, Berenson J, Lipton A. Reduced serum B-cell maturation antigen levels predict poor outcome in metastatic breast cancer patients in a phase 3 randomized 2nd-line hormone therapy trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-10.