Emerging PD-1 and PD-1L inhibitors-associated myopathy with a characteristic histopathological pattern

Matas‐García, Ana; Milisenda, José C.; Selva-O’Callaghan, Albert; Prieto-González, Sergio; Padrosa, Joan; Cabrera, Carlos; Reguart, Noemı́; Anta, Natalia Castrejón de; Solé, Manel; Ros, Javier; Trallero-Araguás, Ernesto; Antoniol, Maria Noelia; Vila-Pijoan, Gemma; Grau, Josep M.

doi:10.1016/j.autrev.2019.102455

Cited by 53 publications

(41 citation statements)

References 18 publications

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“…Better characterization of myositis-like syndromes is available through case series of patients [39][40][41][42]. Clinical data derived from these studies confirm the early onset of the syndrome following only a few infusions of ICI therapy, as well as the frequent concomitant presence of myasthenia-like features and cardiac involvement.…”

Section: Myositismentioning

confidence: 87%

“…Of note, an ICI-induced myasthenia gravis case series [43] also gives an interesting perspective, since these patients exhibited a more severe disease course, lower frequency of autoantibody (such as the anti-acetylcholine receptor antibodies) positivity and greater proportion of concurrent myositis features compared to idiopathic myasthenia gravis patients. Histopathologic data [39,41,42] reveal a specific pattern: myofiber necrosis, macrophage and T cell infiltration with relative absence of B cells. These findings are also present in the myocardium [42,44,45].…”

Section: Myositismentioning

confidence: 99%

“…Histopathologic data [39,41,42] reveal a specific pattern: myofiber necrosis, macrophage and T cell infiltration with relative absence of B cells. These findings are also present in the myocardium [42,44,45]. It seems that cases of ICI-induced myositis may have distinct pathogenesis, yet to be fully understood.…”

Section: Myositismentioning

confidence: 99%

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Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Μελισσαρόπουλος

Klavdianou

Filippopoulou

et al. 2020

IJMS

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

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Section: Myositismentioning

confidence: 87%

Section: Myositismentioning

confidence: 99%

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Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Μελισσαρόπουλος

Klavdianou

Filippopoulou

et al. 2020

IJMS

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“…In studies of inflammatory arthritis as an IRAE, ≥50% of patients experienced additional IRAEs (18). For patients with suspected myositis, history should also be evaluated to identify symptoms of myasthenia or myocarditis, as these IRAEs can accompany each other (23,24).…”

Section: Approachmentioning

confidence: 99%

“…Myofascial inflammation was actually more common than synovitis according to one MRI study of patients receiving ICIs who had musculoskeletal symptoms, so it should be considered when there is pain around the joint rather than centered on the joint (34). Muscle biopsies have shown 2 major patterns: endomysial lymphocytic inflammation and perivascular macrophagic infiltration, both of which can be accompanied by necrosis (23,26,35,36).…”

Section: Physical Examinationmentioning

confidence: 99%

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Cappelli

Bingham

2021

Arthritis & Rheumatology

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Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs. Clinical challenge You receive a consult from a local oncologist. A 65-yearold man with a history of knee osteoarthritis (OA) who had previously undergone total joint arthroplasty of the left knee and is being treated with nivolumab (anti-programmed death 1 [anti-PD-1] monoclonal antibody) for non-small cell lung cancer has new symptoms of severe aching in his arms and legs, with limited mobility. The oncologist does not localize symptoms to the joints and/or muscles but notes that the patient is having trouble doing chores around the house such as cleaning and cooking.

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Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

et al. 2021

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Background. The development of immune checkpoint inhibitors (ICI) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immunerelated adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature. Methods. Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.Results. A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICI (38%). The most-reported symptom was fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. 60% of the patients died in hospital due to acute complications. Conclusion. IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition. The Oncologist ;9999:• •

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Emerging PD-1 and PD-1L inhibitors-associated myopathy with a characteristic histopathological pattern

Cited by 53 publications

References 18 publications

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

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