Use of abatacept in steroid refractory, immune checkpoint‐induced myocarditis

Mathai, Vinod Kalapurackal; Black, Allison; Lovibond, Sam; Lipton, Jonathan; Moldovan, Cristina

doi:10.1111/imj.15566

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…1-3 40 133 Literature review There is limited available evidence regarding the management of steroid-resistant myocarditis. We have identified 15 publications of which 13 publications [134][135][136][137][138][139][140][141][142][143][144][145][146] were case reports, 2 publications were smaller case series with 4 patients 147 and 16 patients 148 and one study included a study population of 30 patients treated with additional immunosuppressive agents 149 (see online supplemental appendix table 8). All the included publications suggested blood analysis, ECG and echocardiography as the first diagnostic approach.…”

Section: Consensus Guidelinesmentioning

confidence: 99%

“…All the included publications suggested blood analysis, ECG and echocardiography as the first diagnostic approach. [134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149] Four publications recommended in addition conducting a cardiac MRI 134 136 137 139 149 or gallium-68 DOTATOC imaging 146 and eight publications the visualization of the coronary vessels by using imaging or percutaneous catheters. 134 136 138 140-143 145 149 Only in two publications was a cardiac biopsy carried out as a diagnostic procedure in all or at least some study patients.…”

Section: Consensus Guidelinesmentioning

confidence: 99%

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Corticosteroid-resistant immune-related adverse events: a systematic review

Daetwyler,

Wallrabenstein,

König

et al. 2024

J Immunother Cancer

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Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient’s immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend—as first line treatment—(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.

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Section: Consensus Guidelinesmentioning

confidence: 99%

Section: Consensus Guidelinesmentioning

confidence: 99%

Corticosteroid-resistant immune-related adverse events: a systematic review

Daetwyler,

Wallrabenstein,

König

et al. 2024

J Immunother Cancer

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“…Another strategy is the use of natalizumab (directed against integrins), which proved efficacy in a case of paraneoplastic syndrome [58]. Looking at the therapeutic approaches that are emerging for severe nonneurological irAEs, abatacept (CTLA-4 agonist) proved encouraging results in patients with myocarditis [59,60 ▪ ]. Its use can be especially proposed for the myasthenic syndromes accompanied by myositis and myocarditis.…”

Section: Principles Of Neurological Involvement Immune-related Advers...mentioning

confidence: 99%

Neurological adverse events of immune checkpoint blockade: from pathophysiology to treatment

Cuzzubbo

Carpentier

2022

Current Opinion in Neurology

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Purpose of reviewWe review the recent advances in neurological toxicities of immune checkpoint inhibitors, with a focus on underlying pathophysiologic mechanisms and the implications on their therapeutical management.Recent findingsA growing number of cancer patients benefit from immune checkpoint agents and oncologists are increasingly confronted with these novel autoimmune syndromes. During the last years, further progresses have occurred in this field, notably in the identification of specific clinical patterns, such as the association of myasthenic syndrome with myositis and myocarditis, and polyradiculoneuropathies accompanied by cerebrospinal fluid lymphocytic pleocytosis. In addition, recent immune-histological studies improved the understanding of the pathophysiologic mechanisms behind immune-related neurotoxicities.SummaryNeurological toxicity is rare compared with other organs and systems, but its potential morbidity and mortality requires a prompt management. If there is a consensus for steroids as a first-line treatment, no exhaustive clinical data exist for other treatments. Recent advances in the knowledge of pathophysiological mechanisms (behind these toxicities) should be taken into account for the management of these patients. Drugs targeting T-cell mediated inflammation should be preferred in patients who are refractory to steroids, whereas therapies targeting humoral mechanisms should be considered in specific cases associated with autoantibodies such as immune-related myasthenic syndrome.

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Multiple drugs

2022

Reactions Weekly

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Use of abatacept in steroid refractory, immune checkpoint‐induced myocarditis

Cited by 3 publications

References 4 publications

Corticosteroid-resistant immune-related adverse events: a systematic review

Corticosteroid-resistant immune-related adverse events: a systematic review

Neurological adverse events of immune checkpoint blockade: from pathophysiology to treatment

Multiple drugs

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