A 33-year-old woman with a history of a stage IIIB melanoma treated by resection and left axillary dissection 3 years previously was referred to the melanoma oncology clinic with surveillance-detected pulmonary and brain metastases. CT imaging identified multiple bilateral pulmonary metastases (maximum diameter 22 mm). MRI head identified a 13 × 11 mm enhancing lesion at the grey–white matter junction of the right posterior cingulate cortex, with surrounding vasogenic oedema (Figure 13.1A), and a further 8 mm diameter lesion in the right inferior temporal lobe. She was asymptomatic, her performance status was 0, and she had no comorbidities and no regular medications other than an oral contraceptive (ethinylestradiol/drospirenone). Treatment with pembrolizumab was initiated (2 mg/kg, every 3 weeks).
After four cycles of pembrolizumab, a restaging CT scan demonstrated an interval reduction in the pulmonary metastases (maximum diameter from 22 mm to 5 mm), and MRI demonstrated a reduction in the parietal metastasis (maximum diameter from 13 mm to 4 mm) (Figure 13.1B), with the right inferior temporal metastasis no longer visible. After cycle 5, her hair turned white. After cycle 7, she complained of increasing fatigue, which was associated with elevated thyroid-stimulating hormone (120 mIU/l), for which levothyroxine was commenced. From cycle 18, she developed symmetrical depigmentation affecting the back of her hands and neck.
At cycle 20, she developed dry, pruritic and painful tight skin on the lateral aspects of her neck, chest, upper arms and thighs that progressed rapidly and began to limit neck movement. On examination, the skin was shiny, indurated and thickened (Figure 13.1C). In addition, the symmetrical depigmentation began to involve her upper arms and thighs. There was no eye, mouth or genital involvement and no respiratory or gastrointestinal symptoms. Histology from a deep incisional biopsy from her right arm was consistent with a diagnosis of localized scleroderma (also termed morphoea). Autoantibody screen was negative (including double-stranded DNA, centromere, ribosomal P, proliferating cell nuclear antigen [PCNA], ribonucleoprotein [RNP], Sm, Ro, La, Scl-70, Jo-1, polymyositis/scleroderma [PM/Scl], fibrillarin, RNA polymerase III, Mi-2, NOR-90, Th/To and Ku). Spirometry was normal (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC]). The combination of localized scleroderma, xerosis cutis and vitiligo was consistent with immune-related toxicity generated by pembrolizumab.
How would you manage this patient with pembrolizumab-induced localized scleroderma?
What is the evidence base for the treatment of immunotherapy-associated scleroderma?
Does pembrolizumab-associated scleroderma generate the same complications as systemic sclerosis?
Are there any risk factors for pembrolizumab-associated scleroderma?