Highlights
- •B-cell proliferation is significantly accelerated in the later stages of mRTX dosing.
- •Closer dynamic B-cell monitoring is required to guide repeated mRTX dosing.
- •Total CD19+ B cells should be below 3% for NMOSD treatment with mRTX.
- •Monitoring total CD19+ B cells and CD27+ memory B cells simultaneously is preferable.
Abstract
Objective
To explore the B-cell proliferation characteristics and monitoring significance under
the modified reduced-dose rituximab (mRTX) regimen for neuromyelitis optica spectrum
disorder (NMOSD).
Methods
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.
Results
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.
Conclusion
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.
Keywords
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Article info
Publication history
Published online: January 16, 2023
Accepted:
January 16,
2023
Received in revised form:
October 2,
2022
Received:
July 12,
2022
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
