Treatment Considerations for Patients with Unresectable Metastatic Melanoma Who Develop Pembrolizumab-Induced Guillain-Barré Toxicity: A Case Report

Abstract

Immunotherapy has improved outcomes in many malignancies, most notably in melanoma, lung cancer, and bladder cancer. Understanding the side effects associated with these medications is an important part of managing our patients. Although fatigue, rash, and diarrhea are commonly reported side effects, it is important to be cognizant of rarer ones, such as neuropathy. Amongst the different neurological toxicities that have been reported in the literature, Guillain-Barré-like neuropathies are quite rare. However, the occurrence of such neuropathies in a patient can be life threatening. The problem this poses in treating cancers such as melanoma is that it eliminates an effective class of medication available to the patient, which can ultimately affect their prognosis. We present a case of a 65-year-old female with unresectable metastatic melanoma who developed Guillain-Barré-like neuropathy after two doses of pembrolizumab. Her clinical course was complicated by three separate hospitalizations over 3 months due to recurring bouts of neuropathy, which resulted in a significant decline in performance status and delay in subsequent treatment of her melanoma. Her prolonged recovery eventually resulted in progression of her melanoma nearly 1 year later, while off therapy. Instead of discontinuing immunotherapy completely, she agreed to a re-challenge with ipilimumab. After one dose, her melanoma regressed and continues to show a sustained response nearly 1 year after treatment without any signs of relapse in her neuropathy. Guillain-Barré toxicity resulting from immune checkpoint inhibition poses a difficult chal-lenge to an oncologist who is determining the next line of treatment for patients with unresectable metastatic melanoma that have progressed while off therapy and who have no targetable mutations. Our case raises the question of whether a re-challenge with a different class of immunotherapy agent is a reasonable option.

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

“…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 average protein level of CSF in patients with GBS related to ICIs was 180.68 ± 152.51 mg/dl (range: 37-680 mg/dl). 63.6% of the cases (21/33) presented with typical albuminocytological dissociation (cells ≤ 5/ μ l and CSF protein > 45 mg/dl) [ 14 , 16 , 20 – 22 , 24 , 28 , 30 – 34 , 38 , 40 – 42 ]. The median value of CSF protein was 124.5 mg/dl (range: 73-680 mg/dl).…”

“…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 ].…”

Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature

“…The diagnostic workup included nerve conduction studies (NCS) and electromyography (EMG) in 18 patients, lumbar puncture in 14 patients, and dosage of serum antibodies of autoimmune neuropathies or paraneoplastic syndromes in eight cases. CSF harbored albuminocytologic dissociation in five cases ( 7 , 10 , 11 , 14 ), while in seven cases, it showed pleocytosis ( 7 , 10 , 12 , 13 , 17 , 18 ), and in two cases, it was normal ( 18 ).…”

“…We identified 24 cases of pembrolizumab-induced neuropathies and/or radiculopathies, mostly reported in small series of single or few patients (Table 2) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Melanoma was the primary tumor in 20 cases, whereas only three patients had lung adenocarcinoma (6,7,16).…”