B-cell-driven relapse and anti-CD20 rescue therapy after Alemtuzumab in RRMS: case report and literature review.

BACKGROUND

Alemtuzumab is an immune reconstitution therapy (IRT) approved for highly active relapsing-remitting multiple sclerosis (RRMS). Notably, the differential reconstitution of B and T cells after alemtuzumab may trigger paradoxical B-cell-mediated inflammation and secondary autoimmunity.

CASE REPORT: We describe the case of a 44-year-old woman with RRMS who experienced a severe, steroid-resistant relapse nine months after her second alemtuzumab cycle. Lymphocyte subtyping revealed disproportionate B-cell repopulation, suggesting a B-cell-mediated immunopathogenesis. Early ocrelizumab switch resulted in rapid clinical and radiological recovery and sustained stability.

LITERATURE REVIEW: We conducted a narrative review of early and paradoxical disease reactivation after alemtuzumab, identifying common features: early onset, poor steroid response, large or tumefactive lesions, and marked B-cell hyperrepopulation. Anti-CD20 therapy often induced rapid remission. These findings may suggest a distinct B-cell-driven mechanism of inflammation. Prior exposure to fingolimod has been observed in several cases, but does not uniformly account for the observed phenotype.

CONCLUSION

This case contributes to the growing evidence that a subset of patients may experience B-cell-driven inflammatory reactivation after alemtuzumab treatment. Lymphocyte subtyping should be performed, and a predominance of CD19+ B cells can guide a timely therapeutic switch to anti-CD20 therapy. Further studies are needed to define whether this represents a distinct post-IRT immunopathological entity.