Obinutuzumab Plus Chlorambucil in a Patient with Severe Myasthenia Gravis and Chronic Lymphocytic Leukemia

Russell, Angela; Yaraskavitch, Megan; Fok, Daniel; Chhibber, Sameer; Street, Lesley

doi:10.3233/jnd-170211

Cited by 15 publications

(10 citation statements)

References 34 publications

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“…Obinutuzumab, an anti-CD 20 monoclonal ab leading mainly to direct cell death of B-cells, was administered to a single patient with chronic lymphatic leukemia and treatment resistant MG, leading to substantial improvement of myasthenic symptoms. 34 …”

Section: B-cell Directed Therapiesmentioning

confidence: 99%

“…33 Obinutuzumab, an anti-CD 20 monoclonal ab leading mainly to direct cell death of B-cells, was administered to a single patient with chronic lymphatic leukemia and treatment resistant MG, leading to substantial improvement of myasthenic symptoms. 34 B-cell proliferation and survival are regulated by B-cell activating factor/a proliferation-inducing ligand (BAFF/APRIL), B-cell activating factor receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activation and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). 35 A phase II study on telitacicept (TACI-Ig fusion protein) in MG is ongoing (NCT04302103).…”

Section: Difficult To Treat or Refractory Mgmentioning

confidence: 99%

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Advances and challenges in the treatment of myasthenia gravis

Schneider‐Gold

Gilhus

2021

Ther Adv Neurol Disord

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Myasthenia gravis (MG) is a chronic autoimmune disease with fluctuating muscle weakness and fatigability. Standard immunomodulatory treatment may fail to achieve sufficient improvement with minimal symptom expression or remission of myasthenic symptoms, despite adequate dosing and duration of treatment. Treatment-resistant MG poses a challenge for both patients and treating neurologists and requires new therapeutic approaches. The spectrum of upcoming immunotherapies that more specifically address distinct targets of the main immunological players in MG pathogenesis includes T-cell directed monoclonal antibodies that block the intracellular cascade associated with T-cell activation, monoclonal antibodies directed against key B-cell molecules, as well as monoclonal antibodies against the fragment crystallizable neonatal receptor (FcRn), cytokines and transmigration molecules, and also drugs that inhibit distinct elements of the complement system activated by the pathogenic MG antibodies. The review gives an overview on new drugs being evaluated in still ongoing or recently finished controlled clinical trials and drugs of potential benefit in MG due to their mechanisms of action and positive effects in other autoimmune disorders. Also, the challenges associated with the new therapeutic options are discussed briefly.

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Section: B-cell Directed Therapiesmentioning

confidence: 99%

Section: Difficult To Treat or Refractory Mgmentioning

confidence: 99%

Advances and challenges in the treatment of myasthenia gravis

Schneider‐Gold

Gilhus

2021

Ther Adv Neurol Disord

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“…Ofatumumab, obinutuzumab, and ocrelizumab are other anti-CD20 agents representing potential future therapeutic alternatives for refractory MG [40][41][42].…”

Section: Direct B Cells Targeting Agentsmentioning

confidence: 99%

Benefit and danger from immunotherapy in myasthenia gravis

et al. 2021

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In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a selective action targeting compounds of the immunological system. This review discusses emerging treatments for MG, including complement inhibitors, neonatal Fc receptor targeting agents, and B cell interfering drugs, focusing on benefit and danger. In the second section of the review, several related adverse events of immunotherapy, including MGonset, are debated.

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“…Whether this difference would be superior for treatment of MG cannot be predicted. There is a single case report of obinutuzumab being used in a patient with treatment-resistant MG and chronic lymphocytic leukemia with success [ 26 ]. Ofatumumab and ocrelizumab are human monoclonal antibodies to CD20 and may have greater cytotoxic potential with fewer adverse effects than rituximab.…”

Section: B-cell Targetingmentioning

confidence: 99%

Monoclonal Antibody-Based Therapies for Myasthenia Gravis

et al. 2020

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Myasthenia gravis (MG) is an autoimmune, neuromuscular disorder that produces disabling weakness through a compromise of neuromuscular transmission. The disease fulfills strict criteria of an antibody-mediated disease. Close to 90% of patients have antibodies directed towards the nicotinic acetylcholine receptor (AChR) on the post-synaptic surface of skeletal muscle and another 5% to the muscle-specific kinase, which is involved in concentrating the AChR to the muscle surface of the neuromuscular junction. Conventional treatments of intravenous immunoglobulin and plasma exchange reduce autoantibody levels to produce their therapeutic effect, while prednisone and immunosuppressives do so by moderating autoantibody production. None of these treatments were specifically developed for MG and have a range of adverse effects. The extensive advances in monoclonal antibody technology allowing specific modulation of biological pathways has led to a tremendous increase in the potential treatment options. For MG, monoclonal antibody therapeutics target the effector mechanism of complement inhibition and the reduction of antibody levels by FcRn inhibition. Antibodies directed against CD20 and signaling pathways, which support lymphocyte activity, have been used to reduce autoantibody production. Thus far, only eculizumab, an antibody against C5, has reached the clinic. We review the present status of monoclonal antibody-based treatments for MG that have entered human testing and offer the promise to transform treatment of MG.

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Obinutuzumab Plus Chlorambucil in a Patient with Severe Myasthenia Gravis and Chronic Lymphocytic Leukemia

Cited by 15 publications

References 34 publications

Advances and challenges in the treatment of myasthenia gravis

Advances and challenges in the treatment of myasthenia gravis

Benefit and danger from immunotherapy in myasthenia gravis

Monoclonal Antibody-Based Therapies for Myasthenia Gravis

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