Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for treatment of relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS). In the OPERA trials, circulating CD19+ B-cell counts dropped to zero within 14 days of OCR infusion. Median time to repletion, defined as >79 cells/uL, was 72 weeks (range 27-175 weeks). Up to 5% of patients showed B-cell repletion during treatment. We sought to determine the frequency of patients on OCR who have significant B-cell reconstitution at the time of their next 6-month dose, and to determine if there is a correlation between early B-cell reconstitution and disease breakthrough or adverse events (AEs).
As part of the ACAPELLA trial, a prospective study with a primary objective of assessing OCR-associated AEs in a real-world MS population, we sought to evaluate the frequency and duration of early B-cell reconstitution and its relationship to disease activity and AEs.
All subjects receiving OCR at the Elliot Lewis Center since March 2017 who consented to participate had serum immunoglobulin levels, JCV antibody titers, and lymphocyte subsets on the day of each infusion prior to receiving OCR. Subjects were followed prospectively and monitored for the occurrence of infections and other serious adverse events (SAEs).
As of December 2019, 291 patients had been treated with OCR and enrolled in ACAPELLA: 181 had been treated for at least 12 months, 131 had been treated for 18 months, and 84 subjects had reached 24 months. Of the 291 subjects, 207 had CD19 values drawn at an infusion. One hundred eighteen subjects (57%) displayed ≥1 cell/uL: 81 subjects (39%) had between 1-15 cells/uL, 32 (16%) between 16-79 cells/uL, and 5 (2%) >79 cells/uL. Thirteen patients with B-cell reconstitution at 12 months had early reconstitution with future infusions. Two of the subjects with CD19 values >15 cells/uL experienced clinical or MRI relapse, compared to 8 subjects that did not have B-cell reconstitution.
Although many patients displayed some B-cell repopulation prior to their next dose (113 subjects), CD19 counts of >79 cells/uL were uncommon (5 subjects). Subjects with early B-cell reconstitution at one infusion were likely to continue to show early repopulation at future infusions. Thus far, we have found no significant correlation between B-cell repopulation and either disease activity or adverse events.