Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis

Maria Protopapa; Muriel Schraad; Katrin Pape; Falk Steffen; Livia Steenken; Frauke Zipp; Vinzenz Fleischer; Stefan Bittner

doi:10.1016/j.medj.2024.10.006

Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis

Med. 2024 Oct 31:S2666-6340(24)00404-5. doi: 10.1016/j.medj.2024.10.006. Online ahead of print.

Authors

Maria Protopapa¹, Muriel Schraad¹, Katrin Pape¹, Falk Steffen¹, Livia Steenken¹, Frauke Zipp¹, Vinzenz Fleischer¹, Stefan Bittner²

Affiliations

¹ Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
² Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. Electronic address: stefan.bittner@unimedizin-mainz.de.

PMID: 39515320
DOI: 10.1016/j.medj.2024.10.006

Abstract

Background: As B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment.

Methods: Here, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab.

Findings: In our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity.

Conclusions: This case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment.

Funding: This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).

Keywords: B cell-depleting treatment; Translation to patients; late-onset neutropenia; multiple sclerosis; ocrelizumab; ofatumumab.