B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab regimen for NMOSD: A real-world case series study.

Abstract

To explore the B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab (mRTX) regimen for neuromyelitis optica spectrum disorder (NMOSD). NMOSD patients treated with mRTX were recruited, and the percentages of total CD19+ B cells and CD27+ memory B cells were dynamically detected by flow cytometry. The annualized relapse rate (ARR) and expanded disability status scale (EDSS) scores were compared before and after mRTX treatment, and the differences in B-cell values were compared between groups. A total of 34 patients with NMOSD were ultimately enrolled. The EDSS score decreased from 2.5 (1.5, 3.0) to 1.3 (1.0, 2.0), and the ARR decreased from 1.0 (0, 2.0) to 0 (0, 0) (p < 0.001). Relapses occurred in 6 patients, with total CD19+ B-cell percentages of 3.25% (2.7%, 3.7%) and CD27+ memory B-cell percentages of 0.3% (0.2%, 0.3%) at initial relapse. Twenty-eight patients (82.4%) remained relapse-free with 84 doses of mRTX. Before 56 repeated doses, the total CD19+ B cells and CD27+ memory B cells were 4.00% (3.14%, 5.32%) and 0.26% (0.17%, 0.40%), respectively. The mean dosing interval was 9.2 months. Both total CD19+ B cells and CD27+ memory B cells proliferated over time after mRTX use, with significantly faster proliferation rates in the later stages. In 28 relapse-free patients, the mean time to reach 1% for total CD19+ B cells was 210 days, and the mean time to reach 3% was 240 days, with the mean interval from 1% to 3% of 65 days. Twenty-five relapse-free patients had no significant differences in maximum, minimum, and mean B-cell values compared to those of 6 patients with relapse. The high rate of B-cell proliferation under the mRTX regimen indicates that closer dynamic B-cell monitoring is required to guide repeated mRTX dosing. Sustained depletion of total CD19+ B cells targeting < 3% of lymphocytes may be feasible, enabling extended dosing intervals.