Introduction Alemtuzumab is a humanised anti-CD52 monoclonal antibody for the early treatment of relapsing remitting multiple sclerosis (RRMS) that works by inducing T-cell depletion.¹ Alemtuzumab has shown benefit in reducing disease activity, relapse, and MRI lesion activity in clinical trials.² There is emerging evidence of autoimmune related adverse effects that include thyroid disease, nephropathy, and thrombocytopenia.³ Thrombocytopenia secondary to alemtuzumab has been associated with mortality. The pathophysiological mechanism of alemtuzumab-associated thrombocytopenia is yet to be elucidated and treatment efficacy for patients with thrombocytopenia is unclear, ranging from watchful waiting to intravenous immunoglobulin (IVIG). We discuss a four patient case series in regards to alemtuzumab-associated thrombocytopenia.

Methods A retrospective review of a random sample of four patients at one institution with RRMS who had been treated with alemtuzumab and developed thrombocytopenia requiring intervention with either prednisolone, IVIG or romiplostim.

Results We describe four patients with varying degrees of alemtuzumab-associated thrombocytopenia. Patient 1 developed mild thrombocytopenia with response to prednisolone. Patient 2 developed moderate thrombocytopenia and responded to methylprednisolone and prednisolone. Patient 3 developed fluctuating thrombocytopenia that required prednisolone. This patient then developed severe thrombocytopenia with clinical evidence of purpura. A bone marrow biopsy was undertaken and romiplostim was started with platelet recovery. Patient 4 developed severe thrombocytopenia refractory to prednisolone and IVIG. Romiplostim was initiated with platelet recovery.

Conclusion The pathophysiology of alemtuzumab-associated thrombocytopenia is incompletely understood and may include both a central immune tolerance checkpoint failure of platelet self-antigens and potentially peripheral immune mechanisms.⁴ Treatment of alemtuzumab-associated thrombocytopenia under the assumption that the mechanism is primarily similar to immune thrombocytopenic purpura may be incorrect, and thrombopoietin receptor agonists may have a role.

References

1. . Sprenger, et al. Alemtuzumab: who and when to treat?Comment in the Lancet 2012;380:1795–1797.

2. . Cohen, et al. Alemtuzumab versus interferon beta 1a as first line treatment for patients with relapsing-remitting multiple scleorsis: A randomised controlled phase 3 trial.The Lancet 2012;380:1819–28.

3. . Havroda, et al. Understanding the positive benefit: risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical development program. Therapeutics and Clinical Risk management 2017:13:1423–1437.

4. . Fogarty, et al. ITP: Tolerance Lost. Blood 2011;118(24):6232–6233.