Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature

Abstract

BackgroundMyasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication.MethodsWe reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases.ResultsSixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011).ConclusionsMG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.

Myasthenia gravis and concurrent myositis following PD-L1 checkpoint inhibitor for non-small cell lung cancer

“…Muscle disorders are the second most common association in 0.58%–0.76% 8. A concurrent diagnosis of ICI-induced MG and myositis has been reported in 37% and myocarditis in 8% of a large series of patients with ICI-induced MG 6. ICI-induced MG usually occurs within the first to fifth infusion 9.…”

“…Recommendations vary regarding as to whether ICIs should be discontinued after diagnosis of ICI-induced MG. In the largest series of patients with ICI-induced MG, the ICI was discontinued in most (97%) and readministration was reported for six patients after stabilisation of MG symptoms 6. All of these patients were maintained on prednisone, pyridostigmine and/or intravenous immunoglobulin at the time of ICI readministration 6.…”

“…MG, an autoimmune disorder of neuromuscular junction, has been reported in association with several ICIs including atezolizumab, pembrolizumab, nivolumab and ipilimumab 2–5. Over one-third of ICI-associated patients with MG may have a concurrent myositis and myocarditis may also occur 6. In addition ICI-associated myositis may rarely present with limited involvement to the facial and extraocular muscles and even mimic MG 7.…”

Pathomechanisms and Clinical Implications of Myasthenic Syndromes Exacerbated and Induced by Medical Treatments

“…Of note, almost half of the patients in this study rapidly developed respiratory failure requiring mechanical ventilation. Characteristic laboratory features were positive AChR Abs in 66%, anti-striated Abs in 67% and elevated CK levels in 84% (Safa et al, 2019). To the best of our knowledge, auto-Abs against the muscle-specific kinase (MuSK) have so far only been reported in one single case under nivolumab (occurring together with AChR Abs) (Mitsune et al, 2018).…”

“…Steroids are often used as first-line treatment approach, followed by immune-modulatory agents in refractory cases (Choi and Lee, 2020). However, the data presented by Safa et al support the early use of intravenous immunoglobulins (IVIg) and plasma exchange (PLEX), leading to improved outcomes compared to steroids alone (Safa et al, 2019). The response to a symptomatic treatment with cholinesterase inhibitors seems to be variable (Johansen et al, 2019).…”