Luca Diamanti1, Alberto Picca2, Paola Bini1, Matteo Gastaldi1, Enrico Alfonsi1, Anna Pichiecchio1, Eugenia Rota3, Roberta Rudà4, Francesco Bruno5, Veronica Villani6, Edvina Galiè6, Alberto Vogrig7, Mariarosaria Valente7, Marco Zoccarato8, Valentina Poretto9, Bruno Giometto9, Carolina Cimminiello10, Michele Del Vecchio10, Enrico Marchioni1. 1. "C. Mondino" National Neurological Institute, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy. 2. "C. Mondino" National Neurological Institute, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy. picca.alberto@gmail.com. 3. Neurology Unit, Ospedale San Giacomo, Novi Ligure, ASL Alessandria, Italy. 4. Castelfranco Veneto Hospital, Castelfranco Veneto, Italy. 5. University and City of Health and Science of Turin, Turin, Italy. 6. IRCCS Regina Elena National Cancer Institute, Rome, Italy. 7. Clinical Neurology Unit, Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine, Italy. 8. UOC Neurologia O.S.A. - Azienda Ospedale Università Di Padova, Padua, Italy. 9. Department of Emergency, Neurology Unit, Santa Chiara Hospital, Trento, Italy. 10. Medical Oncology, IRCCS National Cancer Institute, Milan, Italy.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.
Authors: S Cuzzubbo; F Javeri; M Tissier; A Roumi; C Barlog; J Doridam; C Lebbe; C Belin; R Ursu; A F Carpentier Journal: Eur J Cancer Date: 2017-01-05 Impact factor: 9.162
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