BLOOMS
Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab
Clinical Question
In patients with relapsing MS treated with CD19+ B-cell guided extended interval dosing of ocrelizumab, is time to B-cell repopulation stable within an individual across successive doses?
Study Overview
Objective
To determine the intra-individual variability of time to CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing in relapsing MS, as a subgroup analysis of the ongoing BLOOMS randomised trial.
Study Summary
- Time from last ocrelizumab dose to CD19+ B-cell repopulation ≥ 0.01 × 10^9 cells/L varied widely between individuals (range 20.6–72.1 weeks; mean 32.8 ± 7.0)
- Within individuals, however, the repopulation interval was highly stable: median coefficient of variation 5.6% (IQR 3.1–8.4), equivalent to ~2 weeks variation per dosing interval
- 87.8% of participants had ≤ 10% intra-individual variation across dosing intervals; sensitivity analysis in those with ≥3 intervals confirmed the finding (CV 5.9% vs 5.6%)
- Only one clinical relapse was reported during follow-up (in a participant with a mean interval of 28 weeks, CV 9.8%)
Intervention
CD19+ B-cell guided extended interval dosing of intravenous ocrelizumab 600 mg (redosed within 4 weeks of CD19+ B-cell count exceeding ≥ 0.01 × 10^9 cells/L, measured monthly from 24 weeks after last infusion).
Patients per Arm
B-cell guided dosing subgroup: n=75 (209 dosing intervals)
Bottom Line
Although time to CD19+ B-cell repopulation after ocrelizumab varies widely between individuals (20.6–72.1 weeks), it is remarkably stable within each individual (median intra-individual CV 5.6%, ≈2 weeks per dosing interval), supporting the feasibility of personalised B-cell guided extended interval dosing.
Major Points
- Prospective subgroup analysis of the ongoing BLOOMS randomised trial (NCT05296161) in the CD19+ B-cell guided ocrelizumab dosing arm (n=75, 209 dosing intervals; 22 Dutch centres).
- Time from last dose to first CD19+ B-cell count ≥ 0.01 × 10^9 cells/L ranged 20.6–72.1 weeks (mean 32.8 ± 7.0), confirming large inter-individual variability.
- Within individuals, the interval was highly stable: median coefficient of variation 5.6% (IQR 3.1–8.4), corresponding to ~2 weeks variation per dosing cycle.
- 87.8% of participants had ≤10% intra-individual variability across intervals; findings persisted in the subgroup with ≥1 extended interval ≥28 weeks (CV 5.7%) and in sensitivity analysis of participants with ≥3 intervals (CV 5.9%).
- 80% of participants received an extended interval ≥28 weeks at least once; only 1 clinical relapse was reported during follow-up.
- Supports feasibility of long-term, personalised B-cell guided interval dosing pending non-inferiority confirmation from the main BLOOMS trial.
Design
Study Type: Prospective cohort / subgroup analysis of an ongoing 1:1 randomised controlled trial (BLOOMS) comparing standard vs CD19+ B-cell guided ocrelizumab dosing
Randomization: 1
Blinding: not reported
Allocation: 1:1 randomisation to standard dosing (600 mg every 6 months) vs CD19+ B-cell guided interval dosing in the parent BLOOMS trial; this analysis includes only participants randomised to B-cell guided dosing
Enrollment Period: not reported (data cutoff August 2025)
Follow-up Duration: Up to five B-cell tailored dosing intervals per participant
Centers: 22
Countries: Netherlands
Sample Size: 75
Analyzed: 75
Analysis: Descriptive; intra-individual variability quantified as coefficient of variation (SD/mean × 100%) of interval durations per participant; sensitivity analyses in participants with ≥3 intervals and in those with at least one interval ≥28 weeks; R Studio 4.3.2
Power Calculation: not reported
Registration: ClinicalTrials.gov NCT05296161
Inclusion Criteria
- Relapsing-onset MS by 2017 McDonald criteria
- Completion of two full ocrelizumab dosing cycles
- Clinically stable disease for ≥3 months prior to inclusion
- Randomised to CD19+ B-cell guided interval dosing arm of BLOOMS
- ≥2 B-cell guided dosing intervals during follow-up
Exclusion Criteria
- Prior treatment with alemtuzumab
- Prior treatment with cladribine
- Prior stem cell transplantation
Arms
| Field | CD19+ B-cell guided interval dosing of ocrelizumab | Control |
|---|---|---|
| N | 75 | |
| Intervention | Ocrelizumab 600 mg IV, redosed within 4 weeks after CD19+ B-cell count exceeded the re-dosing threshold ≥ 0.01 × 10^9 cells/L; CD19+ B-cells measured monthly starting 24 weeks after last dose | Ocrelizumab 600 mg IV every 6 months |
| Duration | Up to five B-cell tailored dosing intervals per participant (209 intervals total) | not reported |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Intra-individual variability of the time interval between last ocrelizumab infusion and first CD19+ B-cell repopulation ≥ 0.01 × 10^9 cells/L, expressed as the coefficient of variation (CV) per participant. (Note: this is a subgroup analysis of the ongoing BLOOMS trial; the parent trial's comparison of B-cell guided vs standard 6-monthly dosing is not reported in this paper, and no formal primary/secondary endpoint hierarchy is designated in this substudy.) | Primary | Not applicable (single-arm subgroup analysis) | Median individual CV 5.6% (IQR 3.1–8.4); 87.8% of participants had ≤10% intra-individual variation; mean interval 32.9 ± 6.9 weeks (range 20.6–72.1) | Not applicable (single-arm descriptive analysis; the 5.6% intra-individual CV corresponds to ~1.8 weeks variation at a mean 32.8-week interval, but this is a descriptive translation of variability, not a treatment-effect estimate) | |
| Interval to B-cell repopulation and intra-individual CV in participants with at least one extended interval ≥28 weeks (n=60) | Secondary | Mean interval 35.0 ± 6.2 weeks; median individual CV 5.7% (IQR 3.4–7.7); 88.0% with ≤10% variability | |||
| Sensitivity analysis in participants with ≥3 B-cell guided dosing intervals | Secondary | n=37 overall (n=30 with extended interval); CV 5.9%, confirming the primary finding | |||
| Proportion of participants achieving extended dosing ≥28 weeks at least once | Secondary | 80% (20% had B-cell repopulation above threshold before 28 weeks) | |||
| Clinical relapse incidence during follow-up | Secondary | 1 clinical relapse in a participant with mean interval of 28 weeks (CV 9.8%) | |||
Subgroup Analysis
Analysis in participants with at least one interval ≥28 weeks (n=60) yielded a mean interval of 35.0 ± 6.2 weeks and median CV of 5.7% (IQR 3.4–7.7). Sensitivity analysis in participants with ≥3 intervals (n=37; n=30 in the ≥28-week subgroup) showed CV 5.9%, confirming the primary result.
Criticisms
- Small cohort (n=75) and relatively short follow-up (maximum of five dosing intervals per participant).
- Subgroup analysis of an ongoing trial — the parent BLOOMS non-inferiority result for B-cell guided vs standard 6-monthly dosing is not yet available.
- Re-dosing threshold of ≥ 0.01 × 10^9 cells/L is acknowledged as somewhat arbitrary, though grounded in COVID-era practice and prior literature.
- Whether CD19+ B-cells are the optimal biomarker vs CD27+ memory B-cells remains unresolved.
- Known temporal predictors (age, cumulative dose) may erode intra-individual stability over longer treatment durations than assessed here.
Funding
ZonMw (No. 848044001) and TreatMeds.
Based on: BLOOMS (European Journal of Neurology, 2026)
Authors: Hogenboom L, Schoof LG, Gelissen LMY, ..., Adriani KS
Citation: Hogenboom L, et al. Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab. Eur J Neurol. 2026;33(7):e70695.
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