Anti-CD20 therapies do not fully resolve chronic, active/smoldering lesions, visible on MRI as paramagnetic rim lesions (PRL), after 2 years of follow-up. These findings may be partially explained by the low numbers of CD20 B cells in chronic active lesions, the limited CD20 B cell tissue turnover, and the inefficient passage of anti-CD20 antibodies across the blood-brain barrier.
B cells play a critical role in MS pathogenesis. B-cell-depleting therapies have generally proven to be effective in relapsing-remitting MS (RRMS) patients and in younger patients with progressive MS (PMS) with disease activity on MRI. This new study aimed to assess the less well-known effects of anti-CD20 antibody therapy on chronic, active/smoldering lesions, visible as PRL. This type of lesion is associated with clinical disease severity and neuro-axonal damage. B-cell lineage lymphocytic subpopulations in chronic, active lesions were also analyzed, including the consequences of their depletion.
To do this, a longitudinal, clinical-MRI study was set up in which 4 European academic hospitals participated. Included were 68 adults with RRMS or PMS; 42 received anti-CD20 treatment, while 26 chose not to be treated. All participants underwent longitudinal 3T susceptibility-based MRI for PRL detection and quantitative-susceptibility-mapping (QSM) analysis. The median follow-up for treated and untreated participants was 26 and 31 months, respectively. Dr. Pietro Maggi (Saint-Luc University Hospital, Belgium) presented the results.
A total of 346 white-matter lesions were studied: 185 PRL (133 treated and 52 untreated) and 161 non-PRL (110 treated and 51 untreated). At follow-up, the paramagnetic rim disappeared in none of the 133-treated PRL. The researchers did not find a significant treatment effect on PRL versus non-PRL for log-lesion volume (P=0.16), Quantitative Susceptibility Mapping (QSM; P=0.56), or T1 values (P=0.34). PRL were larger (P<0.0001) and expanded over time (P=0.009), “confirming their nasty, destructive phenotype,” Dr. Maggi said.
In chronic, active lesions, lymphocytes constituted 6.8% of all immune cells; they included 4.3% of CD20 B cells, 20% of antibody-producing plasmablasts, 75.5% of activated T cells, and 0.2% of natural-killer cells. A gene-regulatory network (GRN) machine-learning analysis predicted that depletion of CD20 B cells, plasmablasts, and T cells would each affect genes highly expressed by microglia and dendritic cells.
- Maggi P. Chronic active multiple sclerosis lesions are poorly responsive to anti-CD20 antibody treatment. Abstract O118, ECTRIMS 2022, 26–28 October, Amsterdam, Netherlands.
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