Thursday, 7 January 2016

ResearchSpeak: L-selectin expression is not a reliable risk factor for the development of PML

Another biomarker fails to translate into clinical practice. #ResearchSpeak #MSBlog #MSResearch

"Earlier reports suggest that a surface marker on T cells predicted PML (progressive multifocal leukoencephalopathy) risk in JC+ve pwMS on natalizumab. The surface marker is called L-selectin and is one of the early adhesion molecules that is responsible for directing, or trafficking, T cells to certain areas of the body. This biology about this finding was quite compelling. The dissappointing news is that in a large study below could not replicate the findings. Why? It may be methodological in that the storage of T cells by freezing may have affected the marker. How the rather blunt conclusion is that this marker is now unlikely to enter routine clinical practice. Therefore the risks factors for developing PML on natalizumab remain the same; i.e. (1) JCV positivity, (2) duration of treatment, (3) previous exposure to immunosuppressive drugs, (4) high anti-JCV antibody index, (5) rising anti-JCV antibody index, (4) and possibly age."


Epub: Lieberman et al. CD62L is not a reliable biomarker for predicting PML risk in natalizumab-treated R-MS patients. Neurology. 2015. pii: 10.1212/WNL.0000000000002314. [Epub ahead of print]

OBJECTIVE: To assess if the percentage of CD3+CD4+CD62L+ cells in cryopreserved peripheral blood mononuclear cells (PBMCs) (here termed %CD62L) can predict risk of developing progressive multifocal leukoencephalopathy (PML) and better inform the physician for benefit-risk assessment of natalizumab treatment decisions in a global setting.

METHODS: Cryopreserved PBMCs from 21 natalizumab-treated patients who developed PML and 104 matched natalizumab-treated patients with multiple sclerosis (MS) without PML collected as a part of Biogen clinical trials were retrospectively examined for CD3, CD4, CCR7, CD45RA, and CD62L by flow cytometry.

RESULTS: In this cohort, %CD62L in natalizumab-treated patients did not predict PML risk. Natalizumab-treated patients with MS without PML showed highly variable %CD62L upon serial sampling. In the STRATA study, the distribution of %CD62L in samples collected more than 6 months before a PML diagnosis, at diagnosis, and in natalizumab-treated patients without PML overlapped. No statistical threshold for risk could be determined. In addition, we demonstrated that lymphocyte viability strongly affects %CD62L, supporting previous reports that %CD62L is inherently unstable following cryopreservation and is sensitive to sample collection.

CONCLUSION: Data from this well-controlled cohort of natalizumab-treated patients indicate that %CD62L is not a biomarker of PML risk.

CoI: multiple

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