Neutropenia complicating anti-CD20 treatment in patients with multiple sclerosis: A retrospective case series and a systematic review of reported cases.

Background: Neutropenia is an infrequent complication of treatment with CD20 depleting agents and may require the administration of granulocyte-colony stimulating factors (G-CSF), which have been associated with an increased relapse risk in patients with multiple sclerosis (PwMS). The management of this side effect is still matter of debate.

Methods: Aim of this study is to evaluate the clinical features and the management of neutropenia occurring in anti-CD20 treated PwMS through a single-center case series and a systematic review of the literature, performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: A total of 19 patients were included (3 from our clinical experience, 16 from the systematic review). Median age was 38 years-old (25-69) and nearly 70% were female, most of these patients had already received a median of 3 (0-4) previous treatments. Neutropenia occurred in 11 patients treated with ocrelizumab and 8 with rituximab, after a median of 2 (1-7) infusions and 9.5 (1-42) months from the first infusion. Most of these patients had late-onset neutropenia, that occurred after a median time of 90 days (2-156). About 70% of patients were symptomatic and most were treated with G-CSF or antibiotics. No relapses after G-CSF were reported. In those who did not suspend anti-CD20 (68.8%), neutropenia reoccurred in 18.2% of cases. Finally, switching between rituximab and ocrelizumab seem not to affect the occurrence of neutropenia.

Conclusion: Our data provides practical evidence regarding the occurrence and the management of neutropenia during treatment with anti-CD20 in PwMS.