Treatment Strategies for CA-LEMS

In this segment, the expert faculty provide a comprehensive overview of contemporary management approaches for Lambert-Eaton myasthenic syndrome (LEMS), emphasizing individualized care based on symptom severity. They explain that while a minority of patients with very mild presentations may experience improvement with cancer-directed therapy alone, most require pharmacologic intervention. Amifampridine (3,4-diaminopyridine) is highlighted as the foundational first-line therapy, functioning by prolonging presynaptic depolarization to enhance calcium channel opening and acetylcholine release. The panel outlines practical dosing strategies, titration schedules, and the point at which insufficient response should prompt escalation to immunomodulatory treatments such as IVIG, plasmapheresis, or corticosteroids. They also discuss longer-term options, including azathioprine, when symptoms remain disabling. Additional nuances include limited benefit and notable side effects of acetylcholinesterase inhibitors, special considerations for patients receiving immune checkpoint inhibitors, and the importance of stabilizing LEMS before immunotherapy. Early data from randomized crossover trials demonstrating functional decline with amifampridine discontinuation further support its central role in management.