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18-12-2023 | Myasthenia Gravis | Brief Communication

Eculizumab for myasthenic exacerbation during treatment with immune-checkpoint inhibitors

Authors: Laura Fionda, Elena Rossini, Antonio Lauletta, Luca Leonardi, Laura Tufano, Rocco Costanzo, Paolo Marchetti, Marco Salvetti, Matteo Garibaldi, Stefania Morino, Giovanni Antonini

Published in: Neurological Sciences | Issue 3/2024

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Abstract

Objective

To test the complement inhibitor eculizumab in the treatment of MG exacerbation during therapy with the immune-checkpoint inhibitor (ICI) pembrolizumab, avoiding its discontinuation, which could be detrimental to oncologic course.

Methods

A 76-year-old male with non-thymomatous generalized anti-AchR + MG (MGFA class IVB), during treatment with pembrolizumab for colorectal cancer, developed a severe myasthenic exacerbation, refractory to steroids and IvIg. Eculizumab was started, without pembrolizumab discontinuation. The patient was prospectively followed using MGFA, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), MG Composite (MGC), and MG Quality of Life 15 (MG-QOL-15).

Results

After an 18-week follow-up, the patient presented a progressive improvement in scores on all scales, achieving a MGFA class IIIB. The percentage improvement was 40% in MG-ADL, 36% in MG Composite, and about 30% in QMG. Bulbar symptoms improved by about 70% in MG-ADL and MG Composite and 40% in QMG. Eculizumab was well tolerated and pembrolizumab regularly continued, with a good control of cancer progression.

Discussion

Eculizumab potentially offers a mechanism-based treatment of MG in patients under anti-programmed cell death protein 1 (PD-1) agents, without interfering with their mechanism of action and avoiding their discontinuation. Larger case series deserve to be evaluated.
Literature
1.
go back to reference Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T (2022) Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol 19(1):37–50CrossRefPubMed Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T (2022) Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol 19(1):37–50CrossRefPubMed
2.
go back to reference Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K et al (2017) Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 89(11):1127–1134CrossRefPubMed Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K et al (2017) Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 89(11):1127–1134CrossRefPubMed
3.
go back to reference Kao JC, Brickshawana A, Liewluck T (2018) Neuromuscular complications of programmed cell death-1 (PD-1) inhibitors. Curr Neurol Neurosci Rep 18(10):63CrossRefPubMed Kao JC, Brickshawana A, Liewluck T (2018) Neuromuscular complications of programmed cell death-1 (PD-1) inhibitors. Curr Neurol Neurosci Rep 18(10):63CrossRefPubMed
4.
go back to reference Marini A, Bernardini A, Gigli GL, Valente M, Muñiz-Castrillo S, Honnorat J et al (2021) Neurologic adverse events of immune checkpoint inhibitors: a systematic review. Neurology 96(16):754–766CrossRefPubMed Marini A, Bernardini A, Gigli GL, Valente M, Muñiz-Castrillo S, Honnorat J et al (2021) Neurologic adverse events of immune checkpoint inhibitors: a systematic review. Neurology 96(16):754–766CrossRefPubMed
5.
go back to reference Majem M, García-Martínez E, Martinez M, Muñoz-Couselo E, Rodriguez-Abreu D, Alvarez R, Arance A et al (2020) SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019). Clin Transl Oncol 22(2):213–222CrossRefPubMed Majem M, García-Martínez E, Martinez M, Muñoz-Couselo E, Rodriguez-Abreu D, Alvarez R, Arance A et al (2020) SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019). Clin Transl Oncol 22(2):213–222CrossRefPubMed
6.
go back to reference Howard JF Jr, Karam C, Yountz M, O'Brien FL, Mozaffar T; REGAIN Study Group (2021) Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses. Ann Clin Transl Neurol 8(7):1398–1407 Howard JF Jr, Karam C, Yountz M, O'Brien FL, Mozaffar T; REGAIN Study Group (2021) Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses. Ann Clin Transl Neurol 8(7):1398–1407
7.
go back to reference Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I et al (2019) Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve 60(1):14–24CrossRefPubMedPubMedCentral Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I et al (2019) Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve 60(1):14–24CrossRefPubMedPubMedCentral
8.
go back to reference Mantegazza R, Wolfe GI, Muppidi S, Wiendl H, Fujita KP, O’Brien FL et al (2021) Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension. Neurology 96(4):e610–e618CrossRefPubMedPubMedCentral Mantegazza R, Wolfe GI, Muppidi S, Wiendl H, Fujita KP, O’Brien FL et al (2021) Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension. Neurology 96(4):e610–e618CrossRefPubMedPubMedCentral
9.
go back to reference Homšek A, Radosavljević D, Miletić N, Spasić J, Jovanović M, Miljković B et al (2022) Review of the clinical pharmacokinetics, efficacy and safety of pembrolizumab. Curr Drug Metab 23(6):460–472CrossRefPubMed Homšek A, Radosavljević D, Miletić N, Spasić J, Jovanović M, Miljković B et al (2022) Review of the clinical pharmacokinetics, efficacy and safety of pembrolizumab. Curr Drug Metab 23(6):460–472CrossRefPubMed
10.
Metadata
Title
Eculizumab for myasthenic exacerbation during treatment with immune-checkpoint inhibitors
Authors
Laura Fionda
Elena Rossini
Antonio Lauletta
Luca Leonardi
Laura Tufano
Rocco Costanzo
Paolo Marchetti
Marco Salvetti
Matteo Garibaldi
Stefania Morino
Giovanni Antonini
Publication date
18-12-2023
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 3/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-023-07190-0

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