Prognostic Value of Serum Beta-2 Microglobulin during and after Completing Chemotherapy in Marginal Zone Lymphoma

Background Baseline serum beta-2 microglobulin (B2M) has been suggested as a prognostic factor for marginal zone lymphoma (MZL). However, there have been no reports on the prognostic value of sequential serum B2M during and after chemotherapy. Herein, we retrospectively reviewed sequential values of serum B2M: baseline (B2M_b), maximum during chemotherapy (B2M_m), end of chemotherapy (B2M_e), and the first increased value after completing chemotherapy (B2M_fi).

Methods Between January 2000, and June 2018, a total of 94 patients with MZL treated with rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) were identified from the database of Asan Medical Center, Seoul, Korea. Respective serum B2Ms less than 2.5 mg/L were considered normal. The cutoff value for differences between serum B2M_b and sequential values of serum B2M were calculated by using the optimal point from the receiver operating characteristic curve.

Results Median age of the study population was 55 year-old (range, 10-83) and 54 (57%) patients were male. Fifteen (16%) patients had nodal MZL, 76 (81%) had extranodal MZL and 3 (3%) had splenic MZL. In univariate analysis, serum B2M_b and B2M_fi above 2.5 mg/L were associated with poor prognosis with a hazard ratio (HR) of 2.3 (95% confidence interval (CI): 1.1-4.9; p=0.024) and a HR of 3.3 (95% CI: 1.6-7.0; p=0.001), respectively. In addition, the difference between serum B2M_b and B2M_fi greater than the optimal cutoff value of 0.6 mg/L (area under curve=0.58) was also associated with poor prognosis, with a HR of 4.0 (95% CI: 1.9-8.3; p<0.001). In multivariate analysis, serum B2M_fi above 2.5 mg/L was the only independent adverse prognostic factor in terms of progression-free survival (PFS) with a HR of 4.0 (95% CI: 1.2-14.1; p=0.023). The median time of serum B2M_fi measurement was 5.6 months from the end of chemotherapy (range, 0.5-25.1 months).

Conclusion To the best of our knowledge, this is the first report of measuring sequential serum B2M, starting from baseline to its first rise after completing chemotherapy in MZL. In MZL patients treated with R-CVP, the first increased serum B2M above 2.5 mg/L after completing chemotherapy is a powerful prognostic factor for PFS.