Before starting a treatment with immune checkpoint inhibitors (ICIs), oncologists must identify potential risk factors, such as previous or concomitant dysimmune disorders, that could favour the development of immune-related adverse events (irAEs). Unfortunately, patients with a history of autoimmune diseases were not included in clinical trials; however, after careful baseline assessment, they are more frequent than expected in common clinical practice. In this case, proper management, early diagnosis, and careful pre- and post-treatment monitoring of irAEs are required [
We report the case of a male patient, a smoker, with a history of chronic obstructive lung disease, atrial fibrillation, hypertension, obesity, chronic plaque psoriasis, and Guillain–Barré syndrome (GBS). The diagnosis of GBS dated back to 2002; during a community-acquired pneumonia, a molecular mimetism between bacterial antigens and gangliosides of the nerves’ myelin sheath led to the development of a severe and rapidly progressive muscle weakness with areflexia, till tetraplegia. Electromyography (EMG) confirmed acute, axonal polyneuropathy, with reduced sensory action potential, supporting the diagnosis of the “acute motor and sensory axonal neuropathy” (AMSAN) type of GBS. The patient was hospitalized and successfully treated with intravenous immunoglobulins; he then underwent upper left lobectomy of the lung, in order to excise a bronchiectasis, which was acting as a reservoir of bacteria. Besides a residual neurological injury to his legs, no recurrences were later observed. The patient also reported a history of moderate-to-severe plaque psoriasis, previously treated with cyclosporine A, which was stopped in 2013.
In February 2015, he underwent surgical resection of cutaneous melanoma of the left gluteus, with the following histopathological features: nodular melanoma, ulcerated, Breslow thickness 9 mm, poorly pigmented, 12 mitoses/mm2, Clark’s level IV, without regression and intra/peritumoral lymphocytic infiltrate pT4b [
From December 11, 2015, to February 19, 2016, 4 induction doses of ipilimumab (3 mg/kg every three weeks) were administered without significant toxicities, except development of cutaneous facial vitiligo on the face; psoriatic plaques remained unchanged, and the patient did not develop new neurological symptoms. A CT scan in March 2016 showed an immune-related response of disease (dimensional reduction and intralesional necrosis) and also detected a pulmonary embolism, treated with low molecular weight heparin. In April 2016, the CT scan showed resolution of pulmonary embolism, and neurological evaluation showed no changes, just like the control EMG that was performed.
In June 2016, the CT scan showed progressive disease to the lymph nodes; therefore, the patient underwent a second-line therapy with pembrolizumab (2 mg/kg every three weeks) (Keytruda®; Merck Sharp & Dohme Limited, Hoddesdon, United Kingdom), with only one dose administered, on July 11. After that, he decided to continue the treatment at an outpatient cancer care center closer to his home. From October to November 2016, he received 3 doses of nivolumab (3 mg/kg every two weeks) (Opdivo®; Bristol-Myers Squibb Pharma EEIG, Uxbridge, United Kingdom), without developing significant toxicities, but he died in December 2016 due to the progression of the disease.
In clinical practice, every patient should be carefully interrogated about the personal and family history of immune disorders because it is one of the few acknowledged risk factors for development of irAEs [
This case report supports the idea that, in some patients, it could be possible to safely administer sequential treatments with ICIs, although a history of preexisting immune disorders is one of the major risk factors for the development of irAEs. The decision-making process should include a proper balance between the safety profile and expectations; alternatives should be discussed with patients and families, whose compliance is fundamental to reach a good clinical outcome.
The authors declare that they have no conflicts of interest.