Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.
Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging.
A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup.
We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%).
Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.
Diamanti L
，Picca A
，Bini P
，Gastaldi M
，Alfonsi E
，Pichiecchio A
，Rota E
，Rudà R
，Bruno F
，Villani V
，Galiè E
，Vogrig A
，Valente M
，Zoccarato M
，Poretto V
，Giometto B
，Cimminiello C
，Del Vecchio M
，Marchioni E
... -
《-》
Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study.
Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival.
This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors.
From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively).
Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment.
The Instituto de Salud Carlos III and the European Union.
Fonseca E
，Cabrera-Maqueda JM
，Ruiz-García R
，Naranjo L
，Diaz-Pedroche C
，Velasco R
，Macias-Gómez A
，Milisenda JC
，Muñoz-Farjas E
，Pascual-Goñi E
，Gállego Perez-Larraya J
，Saiz A
，Dalmau J
，Blanco Y
，Graus F
，Martinez-Hernandez E
，Neuro-ICI-Spain study group
... -
《-》
Severe neuromuscular immune-related adverse events of immune checkpoint inhibitors at national cancer center in Korea.
Neuromuscular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) have been increasingly recognized as a consequence of expanding use of ICIs in advanced cancers. We aimed to evaluate the frequency, phenotypes, rescue treatment, and clinical outcomes of severe neuromuscular irAEs of ICIs at National Cancer Center (NCC), Korea.
Consecutive patients with newly developed severe neuromuscular irAEs (common terminology criteria for adverse events grade 3 or greater) after ICI treatment at NCC in Korea between December 2018 and April 2022 were included by searching neuromuscular diagnostic codes in electronic medical records and/or reviewing neurological consultation documentations.
Of the 1,503 ICI-treated patients, nine (0.6%) experienced severe neuromuscular irAEs; five with pembrolizumab and four with atezolizumab. The patients included five women and four men; their median age at onset was 59 years. The irAEs included Guillain-Barre syndrome (n = 5) and myasthenia gravis (MG) crisis with myositis (n = 4), and developed after a median of one (range 1-5) ICI cycle. The median modified Rankin score (mRS) was 4 (range 3-5) at the nadir. ICIs were discontinued in all patients, and rescue immunotherapy included corticosteroids (n = 9), intravenous immunoglobulin (n = 7), and plasmapheresis (n = 2). Eight patients showed improvements, with a median mRS of 3 (range 1-4); however, one patient (who had MG crisis with myocarditis) died.
In this real-world monocentric study, ICI-induced neuromuscular irAEs were rare but potentially devastating; thus, physicians should remain vigilant to enable prompt recognition and management of irAEs.
Hyun JW
，Kim KH
，Kim SH
，Kim HJ
... -
《-》
Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.
To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes.
We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available.
A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection.
ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.
Aldrich J
，Pundole X
，Tummala S
，Palaskas N
，Andersen CR
，Shoukier M
，Abdel-Wahab N
，Deswal A
，Suarez-Almazor ME
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
