South Tyneside and Sunderland NHS Foundation Trust
Neurology

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0272 - A case series of late onset neutropenia following Ocrelizumab therapy in Multiple Sclerosis (MS) (ID 1918)

Speakers
Presentation Number
P0272
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab, an anti-CD20 monoclonal antibody similar in action to rituximab, has demonstrated efficacy in relapsing and primary progressive MS. Late onset neutropenia (LON) is a rare, but serious side-effect of rituximab occurring in 1.3% of patients. There only 2 reported cases of LON related to ocrelizumab. A single case of grade 4 LON occurred during the phase three studies.

Objectives

Increase awareness of the features of late onset neutropenia and improve risk management of disease modifying treatments.

Methods

We discuss a case series of 3 treatment naive patients with active RRMS who developed severe LON (grade 4) after ocrelizumab treatment in MS specialist centres in the United Kingdom.

Results

A 31y female presented with neutropenic sepsis (neutrophils 0.0) 115 days after her third ocrelizumab infusion, requiring treatment with intravenous antibiotics and granulocyte colony stimulating factor (G-CSF). Subsequent multiple episodes of recurrent grade 4 neutropenia (neutrophils 0.0-0.2) occurred over the next 6 months, often requiring G-CSF treatment. Bone marrow aspiration demonstrated normocellular granulopoiesis.

A 35y male developed neutropenic sepsis (neutrophils 0.2) 119 days after the first ocrelizumab infusion which recovered rapidly with G-CSF. He received the 2nd and 3rd ocrelizumab doses with no recurrence of neutropenia.

A 22y female developed fever and cough with neutropenia (0.28), 150 days after initial treatment with ocrelizumab. She was treated with IV antibiotics and the neutropenia recovered spontaneously.

Conclusions

The 3 cases demonstrate the spectrum of LON with ocrelizumab. The aetiology of LON is poorly understood, but hypothesised to be mediated by autoimmune destruction, neutrophil apoptosis or failure of release from the bone marrow. The normal bone marrow aspirate suggests peripheral consumption. The cases are important to raise the clinical suspicion of this life threatening complication of disease modifying therapy and the need for serial blood monitoring. Further experience is required to understand risk of recurrence and when it is safe to re-challenge with ocrelizumab.

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