Journal of neurology · 2026
Tocilizumab for severe immune checkpoint inhibitor myopathy-myocarditis: acute and long-term outcomes.
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Chaggar Gurpreet, Mulvany-Robbins Bridget, Anaka Matthew, Putko Brendan, Beecher Grayson
Аннотация
BACKGROUND: Immune checkpoint inhibitor (ICI)-myopathy-myocarditis is an immune-related adverse event, with high mortality despite first-line immunosuppression. Emerging data suggest upregulation of the interleukin-6 (IL-6) pathway in ICI-myopathy, raising interest in IL-6 receptor blockade as escalation therapy. We aimed to characterize acute and long-term functional and oncologic outcomes for severe ICI-myopathy-myocarditis, with focus on those treated with tocilizumab after failure of first-line therapy.
METHODS: We performed a retrospective cohort study of patients admitted with severe (Common Terminology Criteria for Adverse Events [CTCAE] grade 3 or 4) ICI-myopathy-myocarditis managed at a Canadian tertiary referral center. Clinical characteristics, investigations, treatment, and functional and long-term cancer outcomes were summarized. Patients were stratified by treatment with tocilizumab after first-line therapy. Primary outcomes were in-hospital mortality and acute-phase survival. Secondary outcomes included functional status at last follow-up, final CTCAE grade, and oncologic response.
RESULTS: Eleven patients were identified. Eight patients received second-line tocilizumab at a median of 13 days after admission; weakness improved in all, but only 4 survived hospitalization. Among acute-phase survivors, median follow-up was 8.1 months, with final median CTCAE grade of 1. Limb strength normalized before oculobulbar weakness. Most survivors demonstrated partial oncologic response, followed by later disease progression at a median 8 months. No patients were rechallenged with ICI therapy.
DISCUSSION: In severe ICI-myopathy-myocarditis refractory to first-line therapy, escalation with IL-6 receptor blockade was temporally associated with limb muscle strength improvement and favorable long-term functional outcomes among survivors. These findings support further evaluation of tocilizumab as second-line therapy in this high-risk population.
METHODS: We performed a retrospective cohort study of patients admitted with severe (Common Terminology Criteria for Adverse Events [CTCAE] grade 3 or 4) ICI-myopathy-myocarditis managed at a Canadian tertiary referral center. Clinical characteristics, investigations, treatment, and functional and long-term cancer outcomes were summarized. Patients were stratified by treatment with tocilizumab after first-line therapy. Primary outcomes were in-hospital mortality and acute-phase survival. Secondary outcomes included functional status at last follow-up, final CTCAE grade, and oncologic response.
RESULTS: Eleven patients were identified. Eight patients received second-line tocilizumab at a median of 13 days after admission; weakness improved in all, but only 4 survived hospitalization. Among acute-phase survivors, median follow-up was 8.1 months, with final median CTCAE grade of 1. Limb strength normalized before oculobulbar weakness. Most survivors demonstrated partial oncologic response, followed by later disease progression at a median 8 months. No patients were rechallenged with ICI therapy.
DISCUSSION: In severe ICI-myopathy-myocarditis refractory to first-line therapy, escalation with IL-6 receptor blockade was temporally associated with limb muscle strength improvement and favorable long-term functional outcomes among survivors. These findings support further evaluation of tocilizumab as second-line therapy in this high-risk population.