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Objective:To investigate the clinical features and treatment status of immune-related myositis (IRM) caused by immune checkpoint inhibitors (ICIs) in order to improve the diagnosis and treatment rate of the disease.Methods:Two cases of IRM combined with the diagnosis and treatment were described and the literature about IRM in the past 10 years was reviewed, and the clinical data of 59 patients were analyzed.Results:IRM was more common in males, with a total of 47 (79.7%). IRM usually occurred after 45 days of medication or after two doses. The clinical manifestations were mainly myalgia and muscle weakness, which were more common in the limbs. The initial symptoms were ptosis and diplopia. Fifty patients (84.7%) had serum creatine kinase (CK) levels higher than twice the upper limit of normal (UNL). In immunological examinations, 18 patients were found to be positive for anti-rhabdoid muscle antibody (AsM-Ab), while most of the myositisspecific antibodies (MSAs) and myositis-associated antibodies (MAAs) were negative. Thirty-four patients (75.6%) had abnormal EMG, and most patients showed myogenic injury. Muscle magnetic resonance imaging (MRI) showed muscle edema and inflammation in 8 patients. Muscle biopsies from 18 (45.0%) patients showed varying degrees of necrotic myofibers. Fifty-seven patients (96.6%) discontinued ICIs after developing IRM, 54(91.5%) received cortico-steroids, and 20(33.9%) received other treatments including intravenous immuno-globulin (IVIG), plasma exchange.Conclusion:IRM can occur in the early stage of ICIs treatment. Electro-myography, muscle MRI and muscle biopsy in suspicious cases can improve the diagnosis rate of the disease. Early use of corticoteroid, IVIG and other immunotherapy can effectively alleviate the disease.
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Resumen El manejo de las reacciones adversas inducidas por los inhibidores del punto de control inmunitario (IPCI) en cáncer, demanda un trabajo multidisciplinario. Revisamos las causas y el curso clínico de las consultas e internaciones debidas a reacciones adversas de los IPCI entre septiembre de 2015 y julio de 2019 en el Instituto Alexander Fleming. Se registraron los datos demográficos, diagnóstico oncológico, reacción adversa y su grado, requerimiento de internación, tratamiento, mortalidad y evaluación de la reexposición. Se registraron 124 reacciones adversas por IPCI en 89 pacientes. Sesenta y ocho recibían monoterapia y 21 terapia combinada. Las manifestaciones cutáneas fueron las más frecuentes, seguidas de las generales, endocrinas (con mayor frecuencia hipotiroidismo), colitis, neumonitis, neurológicas y hepatitis. Fueron graves (grado ≥ 3), 26 toxicidades en 25 pacientes. Se internaron 15, y 6 de ellos requirieron terapia intensiva. Un caso fue fatal. Recibieron glucocorticoides 34 (12 de ellos por vía intravenosa). Un paciente recibió micofenolato y uno inmuno globulina endovenosa. En 20 se discontinuó el tratamiento. Ocho se reexpusieron y uno de ellos debió suspender definitivamente. Se presenta en esta serie de casos nuestra experiencia con el diagnóstico y tratamiento de las reacciones adversas de una familia de drogas cuya utilización ha crecido en los últimos años.
Abstract The management of patients with immune-related adverse events (irAEs) frequently demands a multidisciplinary approach. We reviewed the causes and clinical course of medical visits and admissions at the Instituto Alexander Fleming due to irAEs between September 2015 and July 2019. Demographic data, diagnosis, toxicity and its severity, requirement of admission, treatment, mortality, and evaluation of the re-administration of immunotherapy were collected. We found 124 irAEs in 89 patients. Sixty-eight of them received monotherapy (76.4%) and 21 (23.6%) combination of drugs. Cutaneous manifestations were the most frequent cause of irAEs, followed by general manifestations, endocrine dysfunctions (hypothyroidism the most frequent), colitis, pneumonitis, neurologic dis orders, and hepatitis. In 26 adverse events (in 25 patients), severity grade was ≥ 3. Fifteen were admitted and 6 required ICU admission. One patient died. Thirty-four received glucocorticoids, 12 of them by intravenous route. One patient received mycophenolate and one IVIG. In 20, the treatment was discontinued; 8 were re-exposed, with definitive discontinuation in one patient. In this case series we report our experience in the diagnosis and management of adverse reactions related to a family of drugs whose use has grown in recent years.