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Eculizumab for myasthenic exacerbation during treatment with immune-checkpoint inhibitors

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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.

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Data availability

I state that the data reported in the manuscript are available.

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Acknowledgements

We thank Doctor Steno Rinalduzzi (Department of Neurology and Stroke Unit, San Camillo de Lellis General District Hospital, Rieti, Italy) for referring the patient to the Neuromuscular Unit at Sant’Andrea Hospital, Sapienza University of Rome.

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Authors and Affiliations

  1. Neuromuscular and Rare Disease Centre, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy

    Laura Fionda, Elena Rossini, Antonio Lauletta, Luca Leonardi, Laura Tufano, Rocco Costanzo, Matteo Garibaldi & Stefania Morino

  2. Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology., SAPIENZA University of Rome, Via Grottarossa 1035-1039, 00189, Rome, Italy

    Laura Fionda, Elena Rossini, Antonio Lauletta, Laura Tufano, Rocco Costanzo, Marco Salvetti, Matteo Garibaldi & Giovanni Antonini

  3. IRCCS IDI—Istituto Dermopatico dell’Immacolata, 00167, Rome, Italy

    Paolo Marchetti

  4. Neurology Unit, Sant’Andrea Hospital, 00189, Rome, Italy, Via Grottarossa 1035-1039

    Luca Leonardi, Marco Salvetti & Stefania Morino

Authors
  1. Laura Fionda
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  2. Elena Rossini
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  3. Antonio Lauletta
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  4. Luca Leonardi
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  5. Laura Tufano
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  6. Rocco Costanzo
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  7. Paolo Marchetti
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  8. Marco Salvetti
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  9. Matteo Garibaldi
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  10. Stefania Morino
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  11. Giovanni Antonini
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Contributions

LF, study concept and design, clinical evaluation, analysis and interpretation of clinical data, manuscript writing, responsibility for the integrity of the study; ER, clinical evaluation and database creation, analysis and interpretation of clinical data; AL, LL, LT, RC, data reporter, database creation, critical revision for intellectual content; MS, PM, critical revision of data collection; MG, SM, clinical evaluation, analysis, and interpretation of clinical data, revision of the manuscript for intellectual content; GA, study concept and design, interpretation of clinical data, statistical analysis, manuscript drafting and revising.

All authors have read and approved the submission.

Corresponding author

Correspondence to Laura Fionda.

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Ethics approval

This study was approved by local ethic committee and had been performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Specific national laws were observed.

Conflict of interest

The authors declare no competing interests.

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Fionda, L., Rossini, E., Lauletta, A. et al. Eculizumab for myasthenic exacerbation during treatment with immune-checkpoint inhibitors. Neurol Sci 45, 1243–1247 (2024). https://doi.org/10.1007/s10072-023-07190-0

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  • DOI: https://doi.org/10.1007/s10072-023-07190-0

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