Severe Myositis, Myocarditis, and Myasthenia Gravis with Elevated Anti-Striated Muscle Antibody following Single Dose of Ipilimumab-Nivolumab Therapy in a Patient with Metastatic Melanoma

Abstract

Immune checkpoint inhibitors targeting programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 have improved survival in patients with metastatic melanoma, especially in combination (i.e., ipilimumab-nivolumab). Postmarketing surveillance has identified rare but at times life-threatening adverse effects associated with these agents in combination and as monotherapy, which include myocarditis, myositis, myasthenia gravis (MG), and hepatotoxicity. Further evaluation of immune checkpoint therapy-induced MG identified the rapid clinical progression, prolonged treatment/supportive therapy course, and higher frequency of myasthenic crisis in these patients versus those with idiopathic MG. More rapid incorporation of aggressive treatment options (i.e., intravenous immunoglobulin, plasmapheresis) may be necessary in these cases. Anti-striational antibodies are often detected in individuals with myasthenia gravis and concurrent myositis and myocarditis. A high-index of suspicion is necessary to assist with rapid treatment initiation as these patients can rapidly deteriorate into respiratory compromise. A case of a 78-year-old woman with metastatic melanoma status after combination therapy with ipilimumab-nivolumab that developed transaminitis, myositis, myocarditis, and myasthenia gravis (with positive anti-striational antibodies) five days after the first cycle, is presented. Despite high dose intravenous methylprednisolone and intravenous immunoglobulin treatment, she ultimately entered hospice care eight days after hospital admission, 36 days after her first cycle.

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

“…The diagnostic plans should comprehensively include the evaluation of other organ systems in addition to the performance of traditional diagnostic studies such as RNST, pyridostigmine/edrophonium test, and serology tests for anti-AChR Ab and anti-MuSK Ab. Regarding the seronegative irMG, studies for less common autoantibodies, such as anti-voltage-gated potassium channel Ab, or anti-striatal antibody, including anti-titin Ab, anti-actin Ab, and anti-myosin Ab, may provide more information ( 40 , 43 ).…”

Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management

“…cTnI, cardiac troponin I; cTnT, cardiac troponin T; BNP, brain natriuretic peptide; TTE, transthoracic echocardiogram; ECG, electrocardiogram; CMR, cardiovascular magnetic resonance; CK-MB, creatine kinase-myocardial band; NT-pro BNP, N-terminal pro-brain natriuretic peptide; CPK, creatine phosphokinase; CK, creatine kinase; CRP, C-reactive protein; AChR Ab, acetylcholine receptor antibody; EF, ejection fraction; LV, left ventricular; LVEF, left ventricular ejection fraction; PE, pericardial effusion; MR, mitral regurgitation; AR, aortic regurgitation; BVD, bi-ventricular dilatation; BAD, bi-atrial dilatation; LVD, left ventricle dilatation; RVD, right ventricle dilatation; TR, tricuspid regurgitation; LAFB, left anterior fascicular block; LBBB, left bundle branch block; RBBB, right bundle branch block; LVH, left ventricular hypertrophy; RAE, right atrial enlargement; LAE, left atrial enlargement; GBF, global biventricular failure; LGE, late gadolinium enhancement; EGE, early gadolinium enhancement AF, atrial fibrillation; PAP, pulmonary artery pressure; LVSF, left ventricular systolic function; RVSF, right ventricular systolic function; RHF, right heart failure; CHB, complete heart block; MI, myocardial infarction; MAB, multiple apical thrombi; CAB, complete atrioventricular block(a* = 9 (Norwood et al, 2017; Ganatra and Neilan, 2018; Katsume et al, 2018; Monge et al, 2018; Thibault et al, 2018; Agrawal et al, 2019; Charles et al, 2019; Sakai et al, 2019; Sharma et al, 2019). (b* = 7) (Ederhy et al, 2018; Frigeri et al, 2018; Matson et al, 2018; Agrawal et al, 2019; Charles et al, 2019; Fazel and Jedlowski, 2019; Khoury et al, 2019). (c* = 8) (Johnson et al, 2016a; Arangalage et al, 2017; Chen et al, 2018; Martin Huertas et al, 2019; Salem et al, 2019).…”

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

“…Involvement of other specialists: severe cases of ICI-related myocarditis are anecdotally associated with neuro-muscular irAEs ( Behling et al., 2017 ; Fazel and Jedlowski, 2019 ; Moreira et al., 2019 ), and the involvement of a neurologist in the evaluation of cases where signs or symptoms of myositis are present may be warranted. Moreover, CV irAEs may be associated to irAEs in other districts ( Puzanov et al., 2017 ) and may require multidisciplinary evaluation with endocrinologists, pneumologists, dermatologists, and gastroenterologists.…”