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Objective: To describe the disease course of carryover progressive multifocal leukoencephalopathy (PML) after switching from natalizumab to ocrelizumab in 2 patients with relapsing-remitting MS., Methods: Two case reports with 1 year of follow-up and retrospective longitudinal measurements of serum neurofilament light (NfL) levels and B-cells., Results: PML was diagnosed 78 days (case 1) and 97 days (case 2) after discontinuation of natalizumab. Both patients developed mild immune reconstitution inflammatory syndrome (IRIS) despite B-cell depletion caused by ocrelizumab. NfL levels increased in both patients during PML-IRIS. PML-IRIS lesions stabilized after treatment with mefloquine and mirtazapine, followed by methylprednisolone, and both patients continued therapy with ocrelizumab when B-cells started to repopulate., Conclusions: The clinical course of carryover PML was mild in both patients, suggesting that B-cell depletion possibly did not aggravate PML-IRIS in these 2 patients., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)