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CD62L is not a reliable biomarker for predicting PML risk in natalizumab-treated R-MS patients
Linda A Lieberman1, Wanyong Zeng1, Carol Singh1
1From Discovery Research, Biogen, Cambridge, MA.
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.
Insights
The percentage of CD62L+ T-cells in cryopreserved cells does not predict progressive multifocal leukoencephalopathy (PML) risk in natalizumab-treated patients. This finding is crucial for assessing treatment benefits and risks in multiple sclerosis (MS) management.
Area of Science:
- Immunology
- Neuroscience
- Clinical Trials
Background:
- Natalalizumab is a treatment for multiple sclerosis (MS).
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious risk associated with natalizumab treatment.
- Identifying biomarkers to predict PML risk is crucial for patient safety and treatment decisions.
Purpose of the Study:
- To evaluate if the percentage of CD3(+)CD4(+)CD62L(+) cells (CD62L) in cryopreserved peripheral blood mononuclear cells (PBMCs) can predict PML risk in natalizumab-treated patients.
- To inform benefit-risk assessments for natalizumab treatment decisions globally.
Main Methods:
- Retrospective analysis of cryopreserved PBMCs from natalizumab-treated patients with (n=21) and without (n=104) PML.
- Flow cytometry was used to analyze CD3, CD4, CCR7, CD45RA, and CD62L expression.
- Samples were collected as part of Biogen clinical trials.
Main Results:
- The percentage of CD62L+ T-cells (%CD62L) did not predict PML risk in this cohort.
- Highly variable %CD62L was observed in natalizumab-treated MS patients without PML upon serial sampling.
- The distribution of %CD62L overlapped between patients who developed PML and those who did not, with no identifiable risk threshold.
- Lymphocyte viability significantly affects %CD62L, indicating its instability post-cryopreservation and sensitivity to sample collection.
Conclusions:
- CD62L is not a reliable biomarker for predicting PML risk in natalizumab-treated patients.
- These findings, from a well-controlled cohort, suggest %CD62L should not be used for PML risk stratification in MS management.
