Immune Checkpoint Inhibitor–related Guillain-Barré Syndrome: A Case Series and Review of the Literature

Abstract

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of various malignancies with promising clinical outcomes. Treatment can, however, be accompanied by serious immune-related adverse events. Neurological adverse events like Guillain-Barré syndrome (GBS) are rare but potentially lifethreatening. We present 3 cases of ICI-related GBS; review cases described in current literature, and discuss treatment strategies. Three patients developed GBS after ICI treatment. The first case with pembrolizumab had a fatal outcome despite treatment with multiple regimens, including steroids and intravenous immunoglobulin (IVIg). The other 2 cases with nivolumab-induced and pembrolizumab-induced GBS, respectively, responded well to treatment with IVIg and steroids. In the current literature, a total of 31 other cases were found. Treatment for ICI-related GBS mostly consisted of concurrent IVIg and steroids (44%), which led to clinical improvement in 73%. Most patients recovered with remaining symptoms (68%), while 10 patients developed respiratory failure (29%) and 6 patients (18%) died. ICI-related GBS should be suspected in patients on ICI treatment who develop subacute progressive weakness of the limbs, sensory loss, and areflexia. On the basis of the guidelines recommendations and our review of the literature, we advise first-line therapy with concurrent IVIg 0.4 g/kg/d for 5 days and prednisolone 1-2 mg/kg/d. Discontinuation of immunotherapy after ICI-related GBS is advised.

Guillain‐Barré Syndrome‐Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases

“…The two patients were also excluded. A total of 30 case reports (total patients = 33) were used for final analysis [ 13 – 42 ]. According to the diagnostic criteria of GBS in NINDS, all the above 33 cases were consistent with the features of GBS.…”

“…Of these, four patients received nivolumab in combination with ipilimumab, and one patient received nivolumab in combination with pembrolizumab. In the above cases, the types of tumor the patients suffered from were melanoma ( n = 20) [ 13 , 14 , 16 , 17 , 23 , 24 , 28 , 29 , 31 – 37 , 39 – 42 ], lung tumor ( n = 7) [ 18 , 21 , 25 , 26 , 28 , 30 , 38 ], urinary tumor ( n = 5) [ 13 , 15 , 19 , 20 , 22 ], and nasal cancer ( n = 1) [ 27 ]. The details were summarized in Tables 4 and 5 .…”

“…The subtypes in four cases were equivocal because they showed mixed features of axonal injury and demyelination [ 23 , 31 , 35 , 36 ]. There were also three cases, two with MFS [ 13 , 20 ] and the other with MFS-GBS overlap [ 32 ]. Regrettably, there were two cases of GBS diagnosis with no mention of subtypes [ 13 , 38 , 40 ].…”

“…There were also three cases, two with MFS [ 13 , 20 ] and the other with MFS-GBS overlap [ 32 ]. Regrettably, there were two cases of GBS diagnosis with no mention of subtypes [ 13 , 38 , 40 ].…”

“…After treatment, 24 cases (72.7%) recovered or had only mild residual dysfunction, with two of them rechallenged ipilimumab [ 14 ] or pembrolizumab [ 21 ], and 5 cases had residual mild paresthesia [ 13 , 14 , 26 , 29 , 33 ]. Among the 33 ICIS-related GBS patients, 5 patients developed tumor progression after discontinuation of ICIS treatment, including 4 patients with melanoma [ 14 , 31 , 32 , 37 ] and 1 patient with bladder cancer [ 22 ].…”