Pembrolizumab, an immune checkpoint inhibitor against the programmed death-1 pathway, has been used in combination with acitinib for the first-line treatment of advanced renal cell carcinoma. Neurotoxicity is a rare immune-related adverse event (irAE). The present study reports a case of Guillain-Barre syndrome (GBS) induced by pembrolizumab and sunitinib, and reviews other previous studies to elucidate the clinical characteristics and suitable management of this rare irAE. An advanced renal cell carcinoma patient who received several cycles of pembrolizumab combined with sunitinib developed limb weakness and numbness of the extremities, and was diagnosed with GBS by electrodiagnostic and cerebrospinal fluid examination. The patient improved after treatment with intravenous immunoglobulin along with prednisone. To the best of our knowledge, this is the first case of GBS during treatment with pembrolizumab in combination with sunitinib in advanced renal cell carcinoma.
Programmed death-1 (PD-1) inhibitors, including pembrolizumab and nivolumab, can activate T cells to kill tumor cells by blocking the binding of the PD-1 receptor and programmed death ligand 1 and 2 (PD-L1 and PD-L2) (
A 55-year-old male presented with a right renal mass on CT scan. He was diagnosed with renal clear cell carcinoma with sarcomatoid differentiation after robot-assisted laparoscopic resection of the local mass (
Pembrolizumab is a potent and highly selective fully human IgG4 PD-1 immune-checkpoint inhibitor. Studies have confirmed its efficacy in several types of advanced cancer, such as melanoma, non-small cell lung cancer, head and neck carcinoma and renal cancer (
GBS is an autoimmune-mediated disease in which most patients have prodromal infection. Common infectious pathogens include cytomegalovirus, Epstein-Barr virus, influenza virus, human immunodeficiency virus, mycoplasma,
Sunitinib is a multi-target tyrosine kinase receptor inhibitor targeting vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor-α receptor (PDGFR-α), PDGFR-β, stem cell receptor and colony-stimulating factor 1 receptor, which was approved by the US Food and Drug Administration for the first-line treatment of metastatic renal cell carcinoma, and postoperative adjuvant treatment of renal cell carcinoma with a high risk of recurrence (
Management of irAEs must never be disregarded. In the PubMed database, eight cases of nivolumab and four cases of pembrolizumab causing GBS have been reported (
Not applicable.
No funding was received.
All data generated or analyzed during the present study are included in this published article.
CHa designed the experiments and wrote the initial draft of the manuscript. JM, YZ, YJ, CHu and YW performed the experiments and assisted in the preparation of the manuscript. JM and YZ analyzed the data. CHa, CHu and YW revised the manuscript. All authors read and approved the final manuscript.
Not applicable.
The reported case has been approved by the patient for academic exchange only.
The authors declare that they have no competing interests.
Pathological findings. (A) Pathological analysis of the resected tumor specimen revealing clear cellular renal cell carcinoma (Fuhrman nuclear grade 2) with (B) sarcomatoid differentiation (stain, hematoxylin and eosin). Magnification, x100. Arrows indicate clear cellular renal cell carcinoma (Fuhrman nuclear grade 2) and sarcomatoid differentiation.
CT scanning before combination therapy in March 2018. (A) Spleen metastasis: The arrow indicates the spleen mass. (B) Local recurrence: The arrow indicates right renal mass. (C) Abdominal cavity metastasis: The arrow indicates abdominal cavity mass.
Electrophysiological examinations of motor nerves (scanning speed: 5 ms/D, sensitivity: 10 mV/D). (A) Amplitude of motor waves of right ulnar nerve decreased (wrist: 5.9 mV, above elbow: 4.8 mV). (B) Amplitude of motor waves of right tibial nerve decreased (ankle: 5.4 mV, knee: 4.2 mV). (C) Amplitude of motor waves of left peroneal nerve decreased (Ankle: 1.4 mV, Below knee: 1.2 mV). (D) Amplitude of motor waves of Right peroneal nerve is normal (Ankle: 2.2 mV, Below knee: 2.0 mV). Normal range of the amplitude of motor nerves are as follow: Ulnar nerve: ≥5.0 mV, tibial nerve: ≥4.8 mV and peroneal nerve: ≥2.0 mV. Electrophysiological examinations of sensory waves (Scanning speed: 3 ms/D, Sensitivity: 10 uV/D): The Sensory waves of (E) left superficial peroneal nerve, (F) right median nerve, (G) right superficial peroneal nerve and (H) right ulnar nerve (H) were not induced. Normal range of distal sensory nerve action potential: Median nerve: ≥13.86 µV; ulnar nerve: ≥10.77 µV; and sural nerve: ≥7.71 µV.
CT scanning after combination therapy in August 2018. (A) Arrow indicates the enhancement degree of spleen metastases was reduced. (B) Arrow indicates the right renal mass has disappeared. (C) Arrow indicates the abdominal cavity metastasis has disappeared.
Literature regarding GBS induced by PD-1 inhibitors.
Study | Disease type | Checkpoint inhibitors | GBS treatment | Outcome | CSF | (Refs.) |
---|---|---|---|---|---|---|
Fukumoto |
NSCLC | Nivolumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Gu |
Melanoma | Nivolumab+ ipilimumab | IVIG, steroids, plasma exchange, mycophenolate | Alive | Albuminocytologic dissociation | ( |
Jacob |
NSCLC | Nivolumab | IVIG, plasma exchange | Dead | Albuminocytologic dissociation | ( |
Kyriazoglou |
Bladder cancer | Nivolumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Nukui |
Nasal cancer | Nivolumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Schneiderbauer |
Melanoma | Nivolumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Supakornnumporn |
Melanoma | Nivolumab+ ipilimumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Thapa |
NSCLC | Nivolumab | IVIG, steroids | Alive | Normal | ( |
Manam |
NSCLC | Pembrolizumab | IVIG, steroids, plasma exchange | Alive | Albuminocytologic dissociation | ( |
Manam |
Melanoma | Pembrolizumab-dabrafenib and trametinib | IVIG, steroids, plasma exchange | Dead | Albuminocytologic dissociation | ( |
de Maleissye |
Melanoma | Pembrolizumab | IVIG, steroids | Alive | Albuminocytologic dissociation | ( |
Ong |
NSCLC | Pembrolizumab | IVIG, steroids | Alive | Unknown | ( |
PD-1, programmed death-1; GBS, Guillain-Barre syndrome; CSF, cerebrospinal fluid; NSCLC, non-small cell lung cancer; IVIG, intravenous immunoglobulin.