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In “Prospective validation of the PML risk biomarker l-selectin and influence of natalizumab extended intervals,” Schwab et al. reported that natalizumab is associated with reduction in l-selectin (CD62L) values and an increase in risk of PML but that cessation of natalizumab or extension of treatment intervals leads to recovery of CD62L values, which could potentially decrease risk of PML. Tugemann commented that the sensitivity of this biomarker was affected by inclusion of samples from patients who developed PML—which could falsely increase results about the sensitivity of the marker—and patients who were JC virus (JCV)-negative, which could falsely decrease results about the sensitivity of the marker. Therefore, Tugemann believes that the analysis should have been restricted to patients who were JCV-positive without PML. Schwab et al. responded that (1) because this study was conducted prospectively, they were not aware of PML diagnosis when they processed the samples but that this mirrored a real-world scenario in which a clinician would send the biomarker without knowing a patient had PML, only to subsequently make the diagnosis and (2) they did not have JCV data for all patients. Despite these limitations, they emphasized the utility of CD62L values to stratify risk for PML and to assist with decision-making about the timing of natalizumab dosing, recognizing that the challenging methodology precludes widespread use. Thus, most clinicians will still have to resort to risk stratification for natalizumab use based on duration of treatment, exposure to other immunosuppression regimens, and JCV positivity.
In “Prospective validation of the PML risk biomarker l-selectin and influence of natalizumab extended intervals,” Schwab et al. reported that natalizumab is associated with reduction in l-selectin (CD62L) values and an increase in risk of PML but that cessation of natalizumab or extension of treatment intervals leads to recovery of CD62L values, which could potentially decrease risk of PML. Tugemann commented that the sensitivity of this biomarker was affected by inclusion of samples from patients who developed PML—which could falsely increase results about the sensitivity of the marker—and patients who were JC virus (JCV)-negative, which could falsely decrease results about the sensitivity of the marker. Therefore, Tugemann believes that the analysis should have been restricted to patients who were JCV-positive without PML. Schwab et al. responded that (1) because this study was conducted prospectively, they were not aware of PML diagnosis when they processed the samples but that this mirrored a real-world scenario in which a clinician would send the biomarker without knowing a patient had PML, only to subsequently make the diagnosis and (2) they did not have JCV data for all patients. Despite these limitations, they emphasized the utility of CD62L values to stratify risk for PML and to assist with decision-making about the timing of natalizumab dosing, recognizing that the challenging methodology precludes widespread use. Thus, most clinicians will still have to resort to risk stratification for natalizumab use based on duration of treatment, exposure to other immunosuppression regimens, and JCV positivity.
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Author disclosures are available upon request (journal{at}neurology.org).
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