Alemtuzumab: a review of efficacy and risks in the treatment of relapsing remitting multiple sclerosis

Alemtuzumab is a selective humanized monoclonal antibody directed against the CD52 antigen, and has been found to be a powerful treatment for relapsing remitting multiple sclerosis. Alemtuzumab demonstrated high efficacy in several clinical studies. The risk of relapse and sustained accumulation of disability showed significant reduction in the Phase II CAMMS223 and the Phase III clinical trials CARE MS I and CARE MS II. The data presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis confirmed these results. After completion of a 1-year treatment cycle, alemtuzumab showed a sustained effect. Although the efficacy of alemtuzumab has been widely proven, several severe adverse effects have been reported with its use. Infusion-associated reactions, increased risk of infections, and secondary autoimmunity have been associated with alemtuzumab. Autoimmune disease – mainly of the thyroid – has been reported. Immune thrombocytopenic purpura and autoimmune nephropathies have been observed less frequently. These adverse effects, given the short period of alemtuzumab marketing for relapsing remitting multiple sclerosis, require strict monitoring.

[1]  Jeffrey A. Cohen,et al.  Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial , 2012, The Lancet.

[2]  S. Breslin.  Cytokine-release syndrome: overview and nursing implications. , 2007, Clinical journal of oncology nursing.

[3]  A. Compston,et al.  Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[4]  R. Schmidt,et al.  Cancer therapy-associated CNS neuropathology: an update and review of the literature , 2006, Acta Neuropathologica.

[5]  L. Durelli,et al.  Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab , 2017, Multiple sclerosis.

[6]  T. Tanizawa,et al.  Disseminated necrotizing leukoencephalopathy following chemoradiation therapy for acute lymphoblastic leukemia , 2006, Radiation Medicine.

[7]  G. Hale,et al.  Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. , 1983, Blood.

[8]  K. Selmaj,et al.  Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. , 2008, The New England journal of medicine.

[9]  A. Coles,et al.  Mode of action and clinical studies with alemtuzumab , 2014, Experimental Neurology.

[10]  J. Zajicek,et al.  Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis , 2008, Journal of Neurology.

[11]  A. Compston,et al.  Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis , 1994, The Lancet.

[12]  H. Sakamaki,et al.  Disseminated necrotizing leukoencephalopathy following irradiation and methotrexate therapy for central nervous system infiltration of leukemia and lymphoma. , 1993, Radiation medicine.

[13]  D. Margolin,et al.  Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. , 2014, The Journal of clinical endocrinology and metabolism.

[14]  V. Radhakrishnan,et al.  Disseminated necrotizing leukoencephalopathy following low‐dose oral methotrexate , 2007, European journal of neurology.

[15]  D. Margolin,et al.  Prevention and Management of Infusion-Associated Reactions in the Comparison of Alemtuzumab and Rebif(®) Efficacy in Multiple Sclerosis (CARE-MS) Program. , 2015, International journal of MS care.

[16]  Christian Confavreux,et al.  Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial , 2012, The Lancet.

[17]  A. Wilkins,et al.  Thyroid papillary carcinoma after alemtuzumab therapy for MS , 2014, Journal of Neurology.

[18]  W. Brück,et al.  Disseminated necrotizing leukoencephalopathy eight months after alemtuzumab treatment for multiple sclerosis , 2016, Acta Neuropathologica Communications.

[19]  T. Vartanian,et al.  Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis , 2018, Multiple sclerosis.

[20]  Jeffrey A. Cohen,et al.  Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients , 2016, Neurology.

[21]  M. Ban,et al.  IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). , 2009, The Journal of clinical investigation.

[22]  M. Sheikh-Taha,et al.  Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis , 2017, Multiple sclerosis.

[23]  D. Jayne,et al.  SUMMARY OF PRODUCT CHARACTERISTICS , 2014 .

[24]  J. Halper,et al.  Best practices in multiple sclerosis: infusion reactions versus hypersensitivity associated with biologic therapies. , 2010, Journal of infusion nursing : the official publication of the Infusion Nurses Society.

[25]  H. Wiendl,et al.  Simultaneous early-onset immune thrombocytopenia and autoimmune thyroid disease following alemtuzumab treatment in relapsing-remitting multiple sclerosis , 2016, Multiple sclerosis.

[26]  H. Sullivan,et al.  Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial , 2012, Neurology.

[27]  F. Weber,et al.  Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis—Report of Two Cases , 2015, International journal of molecular sciences.

[28]  J. Zajicek,et al.  Melanoma following treatment with alemtuzumab for multiple sclerosis , 2009, European journal of neurology.

[29]  A. Matucci,et al.  Acute infusion reactions induced by monoclonal antibody therapy , 2011, Expert review of clinical immunology.

[30]  D. Annane,et al.  Multifocal necrotizing leukoencephalopathy in septic shock , 2002, Critical care medicine.

[31]  서정헌,et al.  반도체 공정 overview , 2001 .

[32]  T. Korn,et al.  Fulminant Central Nervous System Nocardiosis in a Patient Treated With Alemtuzumab for Relapsing-Remitting Multiple Sclerosis. , 2016, JAMA neurology.

[33]  H. Waldmann,et al.  T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease. , 1994, Bone marrow transplantation.

[34]  J. Lechner-Scott,et al.  Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study , 2017, The Lancet Neurology.

[35]  L. Kasten,et al.  Pregnancy outcomes in patients with active RRMS who received alemtuzumab in the clinical development program , 2015 .

[36]  F. Bagnato,et al.  Alemtuzumab for the treatment of multiple sclerosis , 2018, Expert opinion on biological therapy.

[37]  A. Compston,et al.  Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis , 1999, Annals of neurology.

[38]  A. Compston,et al.  Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[39]  N. Robertson,et al.  Alemtuzumab for Multiple Sclerosis , 2016, Current Neurology and Neuroscience Reports.

[40]  A. Compston,et al.  Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench , 2004, Clinical Neurology and Neurosurgery.

[41]  J. Byrd,et al.  Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  E. Havrdová,et al.  Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use , 2015, Therapeutic advances in neurological disorders.

[43]  Wellbutrin,et al.  Prescribing Information , 2015, European journal of haematology.