Eculizumab for myasthenic exacerbation during treatment with immune-checkpoint inhibitors.

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.
(© 2023. Fondazione Società Italiana di Neurologia.)