Tailoring B cell depletion therapy in MS according to memory B cell monitoring

Abstract

Objective: We wanted to evaluate efficacy on inflammatory parameters of rituximab (RTX)-personalized reinfusion scheme using a memory B cell-based treatment regimen.

Methods: This is a prospective, uncontrolled, open-label study including patients with MS treated with RTX in 2 Italian MS units. All patients were treated with RTX induction, followed by maintenance infusion at the dosage of 375 mg/m², according to memory B cell repopulation (0.05% of peripheral-blood mononuclear cells [PBMCs] for the first 2 years, 0.1% of PBMC for the third year). MS activity was assessed as clinical or MRI activity.

Results: One hundred two patients were included in the analysis. Mean follow-up was 2.40 years (range 0.57-7.15 years). The annualized relapse rate (ARR) was 0.67 in the year before RTX start and decreased to 0.01 in the 3 years after RTX initiation (global ARR). The proportion of patient with MS activity (i.e., relapse or MRI activity) was 63.16% in the year before RTX start and decreased to 8.7% (0-6 months), 1.3% (6-12 months), 0% (12-24 months), and 0% (24-36 months). Annualized RTX infusion rates were 1.67 (95% confidence interval [CI]: 1.43-1.94), 0.76 (95% CI: 0.58-0.98), and 0.78 (95% CI: 0.52-1.12) for the first 3 years after RTX initiation, respectively. Patients were reinfused with a mean infusion interval of 367 days (range 181-839 days).

Conclusion: The results of this study show that the memory B cell-based RTX reinfusion protocol is able to reduce the mean number of RTX reinfusions with persistent reduction of disease activity.

Classification of evidence: This study provides Class IV evidence that for patients with MS, a memory B cell-based RTX reinfusion protocol can reduce the mean number of RTX reinfusions with persistent reduction of disease activity.

Figure 1. Trend of annualized relapse rate in the 2 years preceding rituximab treatment and in the 3 years after rituximab initiation

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Figure 2. Trend of annualized rituximab reinfusion rate in the 3 years after rituximab initiation for the whole population enrolled (blue) and for the 41 patients who have completed at least 3 years of follow-up (red)