RT Journal Article
SR Electronic
T1 Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e200058
DO 10.1212/NXI.0000000000200058
VO 10
IS 1
A1 Farina, Antonio
A1 Villagrán-García, Macarena
A1 Ciano-Petersen, Nicolás Lundahl
A1 Vogrig, Alberto
A1 Muñiz-Castrillo, Sergio
A1 Taillandier, Luc
A1 Michaud, Maud
A1 Lefilliatre, Mathilde
A1 Wang, Adrien
A1 Lepine, Zoe
A1 Picard, Géraldine
A1 Wucher, Valentin
A1 Dhairi, Maroua
A1 Fabien, Nicole
A1 Goncalves, David
A1 Rogemond, Véronique
A1 Joubert, Bastien
A1 Honnorat, Jèrôme
YR 2023
UL http://nn.neurology.org/content/10/1/e200058.abstract
AB Background and Objectives To clinically characterize post–immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab–positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.Methods Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015–2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018–2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.Results Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44–76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5–18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab–positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, p = 0.02) and limbic (54% vs 14%, p < 0.01), brainstem (27% vs 5%, p = 0.02), and dorsal root ganglia (45% vs 5%, p < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, p = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, p < 0.01) and higher mortality (91% vs 46%, p < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, p < 0.01) and higher mortality (26%, p < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.Discussion The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.CTLA4=cytotoxic T-lymphocyte-associated protein 4; DRG=dorsal root ganglia; Hu-ab=Hu antibody; ICI=immune checkpoint inhibitor; LE=limbic encephalitis; mRS=modified Rankin Scale; n-irAE=neurologic immune-related adverse event; NCS=nerve conduction study; PD1=programmed cell death protein 1; PDL1=programmed death-ligand 1; PNS=paraneoplastic neurologic syndrome; SNN=sensory neuronopathy