B-Cell Depletion — A Frontier in Monoclonal Antibodies for Multiple Sclerosis

2017 ◽  
Vol 376 (3) ◽  
pp. 280-282 ◽  
Author(s):  
Peter A. Calabresi
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals Use of B-Cell–Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

2022 ◽  
pp. 10.1212/CPJ.0000000000001147
Author(s):  
Alexandra Galati ◽  
Thomas McElrath ◽  
Riley Bove
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Childbearing Potential ◽  
Pregnancy And Postpartum

AbstractPurposeof Review: There is considerable heterogeneity in the use of B cell depletion in women of childbearing age, likely driven at least in part by the discrepancy between the product labels and what is known about the physiology of IgG1, including breastmilk and placental transfer.Recent Findings:We provide practical considerations on the use of this medication class in women of childbearing potential. We discuss pre-pregnancy planning including vaccinations, safety of B cell depletion during pregnancy as well as postpartum considerations including breastfeeding.Summary:B cell depleting monoclonal antibodies have shown to be effective for pre-pregnancy and postpartum prevention of inflammatory activity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). B cell depleting therapies are large IgG1 monoclonal antibodies which have minimal transfer across the placenta and into breastmilk. Consideration of risks and benefits of these therapies should be considered in counseling women planning pregnancy and postpartum.

B-Cell Depletion and COVID-19 Severity in Multiple Sclerosis: Remaining Challenges

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012754
Author(s):  
Joep Killestein ◽  
Menno M. Schoonheim ◽  
Rhonda R. Voskuhl
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

2020 ◽  
pp. 135245852091837 ◽  
Author(s):  
Edward Fox ◽  
Amy E Lovett-Racke ◽  
Matthew Gormley ◽  
Yue Liu ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Optimal Dose ◽  
Cell Depletion ◽  
Controlled Study ◽  
Lesion Volume ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Anti Cd20

Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies

2017 ◽  
Vol 24 (9) ◽  
pp. 1224-1233 ◽  
Author(s):  
Nicky Dunn ◽  
Alexander Juto ◽  
Malin Ryner ◽  
Ali Manouchehrinia ◽  
Luca Piccoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Clinical Outcomes ◽  
Clinical Relevance ◽  
Cell Depletion ◽  
Enzyme Linked Immunosorbent Assay ◽  
B Cell Depletion ◽  
Serum Samples ◽  
Cross Sectional ◽  
Cell Counts

Background: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. Objective: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. Methods: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house–validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records. Results: ADAs were detected in 37% of relapsing–remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive. Conclusion: Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.

scholarly journals Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1202
Author(s):  
Arnaud C. Drouin ◽  
Marc W. Theberge ◽  
Sharon Y. Liu ◽  
Allison R. Smither ◽  
Shelby M. Flaherty ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Rescue Therapy ◽  
Health Care Team ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Virus Clearance ◽  
Anti Cd20 ◽  
Antibody Cocktail

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient’s family. Current decisions to take revolve around patient’s follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.

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