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

Abstract

ObjectiveWe wanted to evaluate efficacy on inflammatory parameters of rituximab (RTX)-personalized reinfusion scheme using a memory B cell–based treatment regimen.MethodsThis 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.ResultsOne 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).ConclusionThe 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 evidenceThis 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.

Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness

“…( 5 ) This is supported by the results of the recently published study which showed that the memory B cell–based rituximab reinfusion protocol is able to reduce the mean number of rituximab reinfusions with persistent reduction of disease activity. ( 9 ) Similar findings are observed in the present study, where we have not found increased occurrence of relapses despite higher repopulation of B cells.…”

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

“…For this reason, cells within the memory B cell subsets appear to be important targets for disease control, and their depletion and slow repopulation may, in part, account for the long-term disease control seen from short-term treatment cycles with alemtuzumab, cladribine, ocrelizumab and rituximab [2,3,9,10]. Using rituximab to deplete repopulating memory B cells when they reach predefined levels can maintain clinical remission while reducing the frequency of infusions in RA, NMO, MS and other conditions [3,[11][12][13]. Translating this knowledge may help to improve the benefit : risk balance of ocrelizumab [9].…”

The ocrelizumab phase II extension trial suggests the potential to improve the risk: Benefit balance in multiple sclerosis.

“…This strategy is currently being tested in natalizumab with a view to reduce the risk of developing progressive multifocal leucoencephalopathy (17). Furthermore, preliminary studies with rituximab may suggest that dosing to memory B cell population kinetics can reduce dosing frequency whilst maintaining efficacy (18) Despite policies to make trial-data available, trial-information presented at major international conferences are not always followed by peer-reviewed publications (5,19). Therefore, information cannot easily be searched or interrogated by internet engines and fails to become common knowledge and perhaps allows people to be unwittingly exposed to unnecessary safety issues (19).…”