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Review
. 2024 Feb:82:105400.
doi: 10.1016/j.msard.2023.105400. Epub 2023 Dec 22.

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis

David Baker  1 , Angray S Kang  2 , Gavin Giovannoni  3 , Klaus Schmierer  3
Affiliations
Free article
Review

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis

David Baker et al. Mult Scler Relat Disord. 2024 Feb.
Free article

Abstract

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils. Therefore, alternative explanations are needed for the rare occurrence of early and late-onset neutropenia following such treatments. This probably occurs due to alterations in the balance of granulopoiesis and neutrophil removal. Neutrophils are short-lived, and their removal may be influenced by drug-associated infections, the killing mechanisms of the therapies and amplified by immune dyscrasia due to influences on neutropoiesis following growth factor rerouting for B cell recovery and cytokine deficits following lymphocyte depletion. This highlights the small but evident neutropenia risks following sustained B cell depletion with some treatments.

Keywords: Immune dyscrasia; Immunotherapy; Multiple sclerosis; Neutropenia; Polymorphonuclear neutrophil.

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Conflict of interest statement

Declaration of Competing Interest No company was involved in the decision to write the article or had any influence on its content however, we are grateful to Dr. Sarah Buck, Novartis for supplying meeting presentations. Although considered irrelevant, within the past two years: DB has received honoraria from: Merck KGaA, Novartis, Teva. ASK has nothing relevant to declare. GG has received compensation for serving as a consultant or speaker for or have received research support from AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co, Merck KGaA/EMD Serono, Moderna, Novartis, Sandoz, Sanofi and Roche/Genentech. KS has received honoraria and/or grant support from Amgen, Biogen, EMD Serono, Merck KGaA, Novartis, Roche, Sanofi-Genzyme, and Teva.

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