Monitoring B-Cell Recovery Is Key in Treating Neurological Diseases With Rituximab

Antibodies that deplete B cells, including rituximab, have demonstrated efficacy in the treatment of neurological conditions such as progressive multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The efficacy of these treatments hinges on adequate B-cell depletion, but there is a lack of standardization in treatment and monitoring protocols to guide clinical practice.

In order to identify factors that impact repopulation of B cells after depletion therapy in patients with neurological diseases, researchers, reporting their findings in Neurology, Neuroimmunology & Neuroinflammation, analyzed CD19⁺ B-cell counts in neurology patients who had been treated at least 1 time with a B-cell depleting therapy.

The researchers identified patients in the neurology department of a single center in Germany between 2007 and 2017 and used their anonymized data to determine CD19⁺ cell counts obtained by flow cytometry.

In total, 45 patients, with a total of 373 observations, were identified. The majority of patients received treatment for MS or NMOSD, although patients with polyneuropathy, myasthenia, cerebral vasculitis, and other diseases were also included. Forty-two patients received rituximab, and another 3 received ocrelizumab as part of a clinical trial program. Most (71.1%) patients received doses adapted to body surface area (375 mg/m²), while the remaining patients received fixed doses.

The researchers found that 37 patients experienced at least 1 event of CD19⁺ repopulation (CD19⁺ cells rising to a level above 1% of total CD45⁺ lymphocytes after depletion). The earliest repopulation occurred after 108 days, and the latest occurred after 554 days. Patients who had higher body surface area (and dosages ranging from 574 mg to 975 mg) had a higher risk of experiencing repopulation than patients with lower body surface area, even when they received an adapted dose (hazard ratio, 1.015 per cm²; P <.05); with every 10-cm² increase, the time to cell repopulation was reduced by 14 days.

Several patients received more than 1 treatment cycle of rituximab, and 18 patients had sufficient data to compare B-cell repopulation over time in the same patient; the researchers found no clear pattern in B-cell recovery after the first and last treatment.

“It is important to not miss the time point of B-cell repopulation, as this is most likely linked to resurging disease activity, at least in patients with MS and [NMOSD],” write the authors, who note that “monitoring of B cells is recommended with special attendance to [high—body surface area] patients to not miss the early repopulators.” The researchers propose that patients receiving treatment for neurologic diseases be monitored after 2 and 4 months, then biweekly to every 4 weeks thereafter.

Additionally, the researchers say, future investigations of B-cell depleting therapies in neurological diseases should address both dosing protocol and biomarkers beyond CD19⁺ cells in the peripheral blood; potential biomarkers that could prove useful include memory and effector B cells.

Reference

Ellwardt E, Ellwardt L, Bittner S, Zipp F. Monitoring B-cell repopulation after depletion therapy in neurologic patients. Neurol Neuroimmunol Neuroinflamm. 2018;5(4):e463. doi: 10.1212/NXI.0000000000000463.