Anti-CD20 monoclonal antibodies show promise in multiple sclerosis after failed alemtuzumab

Treatment with anti-CD20 monoclonal antibodies appears to be a viable option for patients with relapsing-remitting multiple sclerosis (RRMS) who have uncontrolled disease following the use of alemtuzumab therapy, suggests a study presented at EAN 2024.

“The aim of this study is to describe our experience using anti-CD20 monoclonal antibodies after alemtuzumab treatment failure of patients with multiple sclerosis,” said lead author Dr Ana Llanes Ferrer from the Neurology Department, Hospital Ramón y Cajal, Madrid, Spain.

Ferrer and her team conducted this retrospective study on 12 patients (median age 35.78 years) with high activity RRMS who were treated with anti-CD20 monoclonal antibodies due to a lack of disease control with alemtuzumab. Of these, 75 percent were women. Participants received a median of two cycles of alemtuzumab therapy.

The authors reviewed the clinical and paraclinical data, including lipid-specific oligoclonal IgM bands (LS-OCMB), plasmablasts over total peripheral blood mononucleated cells (PB/PBMC) prior to the first administration of alemtuzumab, B-lymphocytes over total lymphocytes (BL) before anti-CD20 initiation, and light chain neurofilaments in serum (sNfL), at baseline, 6 months, and 1-year follow-up with anti-CD20 treatment. BL threshold was at 15 percent, PB/PBMC at 0.1 percent, and sNfL at 10 pg/ml.

Patients initiated treatment with anti-CD20 monoclonal antibodies due to severe disease exacerbation, as characterized by relapses or new lesions seen on MRI. Of these, nine patients (75 percent) received ocrelizumab, two (16.6 percent) ofatumumab, and one (8.3 percent) rituximab.

Previously, four patients (25 percent) received three or more cycles of alemtuzumab and eight (75 percent) received two cycles. Their Expanded Disability Status Scale prior to anti-CD20 initiation was 2, and the annualized relapse ratio with alemtuzumab was 0.7.

Uncontrolled disease

Three out of 11 patients had a median of seven gadolinium-enhancing lesions at baseline. All 10 patients who underwent lumbar puncture had LS-OCMB (100 percent), six of seven (85.7 percent) had PB/PBMC >0.1 percent, seven of 11 (75 percent) had BL >15 percent at baseline (data of high B-cell activity), and nearly half (4/10, 40 percent) had elevated sNfL, which normalized after 6 months of treatment with anti-CD20 monoclonal antibodies. [EAN 2024, abstract EPO-169]

Participants also had intense radiological activity. Six of 12 patients (50 percent) had more than 50 lesions, five (41.7 percent) had 10‒50, and only one (8.3 percent) had less than 10.

Eleven patients completed the 1-year follow-up, of whom three had new nonenhancing lesions and one had a relapse. None of them had confirmed disability progression. Additionally, 72.7 percent of patients achieved NEDA3*. Four out of 10 patients developed hypogammaglobulinemia, but none of them had serious infections or required hospital admission.

“In our series, anti-CD20 monoclonal antibodies were a safe and effective alternative for RRMS patients with uncontrolled disease after alemtuzumab,” said Llanes.

*no evidence of disease activity-3 (no new or enlarging T2 lesion on MRI)