L-Selectin as a Biomarker for Progressive Multifocal Leukoencephalopathy Risk With Natalizumab Treatment

A reduction of L-selectin (CD62L) on CD4⁺ T cells in patients treated with natalizumab is a biomarker for increased risk for progressive multifocal leukoencephalopathy (PML), according to study results published in Neurology. Extending the treatment intervals or cessation of natalizumab was associated with recovered CD62L values, in line with the lower PML incidence in these patients.

As there are mixed results regarding the importance of CD62L as a biomarker for the development of PML during natalizumab treatment, the researchers assessed the levels of CD62L in natalizumab-treated patients and investigated the effect of extending treatment intervals or cessation of natalizumab.

The observational study included 3786 samples from 1108 patients with multiple sclerosis, including 15 patients with PML, that were prospectively collected between January 2014 and November 2018.

The data show that natalizumab treatment was associated with lowered CD62L levels (effect size=−12.51; P =9.5×10^-13), and cessation of natalizumab was followed by increase to pretreatment levels. The data pointed to 2 optimal thresholds for PML risk prediction: <15.65 (sensitivity, 33.33%; specificity, 89.78%; and likelihood ratio, 3.263) and <36.05 (sensitivity, 86.67%; specificity, 53.51%; and likelihood ratio, 1.864). The lowest CD62L levels from each patient were significantly lower in patients who later developed PML.

Using 1655 samples from 384 patients with available information, the researchers explored the effect of extending natalizumab intervals on PML risk. There was a linearly increase of CD62L levels, reaching pretreatment levels after 8 weeks, indicating that cessation of natalizumab or extension of treatment intervals may lead to recovered CD62L values, which would fit with the lower PML incidence in these patients.

The researchers noted that despite these encouraging data, the biomarker’s complex methodology currently limits widespread usage.

“CD62L might, therefore, be evaluated as a potential biomarker in future studies for balancing efficacy and safety in individualized dosing,” concluded the researchers.

Reference

Schwab N Schneider-Hohendorf T, Pignolet B, et al. Prospective validation of the PML risk biomarker L-Selectin and influence of natalizumab extended intervals [published online August 22, 2019]. Neurology. doi:10.1212/WNL.0000000000008135.