Immune phenotyping study revealing caveats regarding a switch from fingolimod to cladribine

Background: Recent data support a key role of B cells in the pathogenesis of multiple sclerosis. Due to the pronounced effect of cladribine on memory B cells, we initiated an immune phenotyping study, which included monitoring of memory B cells of patients newly assigned to this treatment option. A patient with ongoing disease activity in the first year of cladribine after a long-standing fingolimod treatment caught our attention. Objective: To report about differences in the immune phenotype of the case compared to patients without disease activity and to discuss possible causes for the deviations as caveats regarding treatment sequelae. Methods: Clinical data and immune phenotyping data collected at baseline (before treatment) and after three, six and ten/twelve months after cladribine initiation were compared between our case and six patients with a stable disease course (controls). Results: Both, the case and controls showed similar reductions of memory B cells in response to cladribine. The case however, showed an accelerated repopulation dynamic of n & auml;ve B cells with an almost 3-fold hyperrepopulation compared to baseline levels, and lower pre-treatment levels of CD4+ and CD8+ T cells and memory B cells compared to controls. Conclusion: We propose a prolonged pre-treatment with fingolimod as possible cause for the lack of response to cladribine. Autoreactive cells sequestrated within lymph nodes may have evaded cladribine depletion on top of a delay of recirculating regulatory T cells. In addition, we want to raise awareness of the importance of monitoring T and B cells for bridging the current lack of evidence regarding sequencing therapies in the real life setting.

Automated summary

The study reported differences in the immune phenotype of a patient with disease activity during cladribine treatment compared to patients without disease activity, and discussed possible causes for these deviations as caveats regarding treatment sequelae. Both the case and controls showed similar reductions in memory B cells in response to cladribine, but the case exhibited accelerated repopulation dynamics of naive B cells with almost 3-fold hyperrepopulation compared to baseline levels. Additionally, the case had lower pre-treatment levels of CD4+ and CD8+ T cells and memory B cells compared to controls.