Combination anti-PD1 and ipilimumab therapy in patients with advanced melanoma and pre-existing autoimmune disorders

Background Clinical trials of immunotherapy have excluded patients with pre-existing autoimmune disease. While the safety and efficacy of single agent ipilimumab and anti-PD1 antibodies in patients with autoimmune disease has been examined in retrospective studies, no data are available for combination therapy which has significantly higher toxicity risk. We sought to establish the safety and efficacy of combination immunotherapy for patients with advanced melanoma and pre-existing autoimmune diseases.Methods We performed a retrospective study of patients with advanced melanoma and pre-existing autoimmune disease who received combination ipilimumab and anti-PD1 at 10 international centers from March 2015 to February 2020. Data regarding the autoimmune disease, treatment, toxicity and outcomes were examined in patients.Results Of the 55 patients who received ipilimumab and anti-PD1, the median age was 63 years (range 23–83). Forty-six were treated with ipilimumab and nivolumab and nine with ipilimumab and pembrolizumab.Eighteen patients (33%) had a flare of their autoimmune disease including 4 of 7 with rheumatoid arthritis, 3 of 6 with psoriasis, 5 of 10 with inflammatory bowel disease, 3 of 19 with thyroiditis, 1 of 1 with Sjogren’s syndrome, 1 of 1 with polymyalgia and 1 of 1 with Behcet’s syndrome and psoriasis. Eight (44%) patients ceased combination therapy due to flare. Thirty-seven patients (67%) had an unrelated immune-related adverse event (irAE), and 20 (36%) ceased combination immunotherapy due to irAEs. There were no treatment-related deaths. Patients on immunosuppression (OR 4.59; p=0.03) had a higher risk of flare.The overall response rate was 55%, with 77% of responses ongoing. Median progression free survival and overall survival were 10 and 24 months, respectively. Patients on baseline immunosuppression had an overall survival of 11 months (95% CI 3.42 to 18.58) compared with 31 months without (95% CI 20.89 to 41.11, p=0.005).Conclusions In patients with pre-existing autoimmune disease, not on immunosuppression and advanced melanoma, combination ipilimumab and anti-PD1 has similar efficacy compared with previously reported trials. There is a risk of flare of pre-existing autoimmune disorders, particularly in patients with inflammatory bowel disease and rheumatologic conditions, and patients on baseline immunosuppression

Upper eyelid defect by dog bite reconstructed by an ipsilateral advanced tarsoconjunctival flap with skin graft

A technique for reconstruction of a traumatic upper-eyelid marginal defect utilizing a local tarsoconjunctival advancement flap with a skin graft is presented. A 22-year-old woman was bitten by a dog, resulting in a fullthickness loss of approximately the central half of her left upper eyelid. Debridement was performed under topical anaesthesia followed by one-stage upper eyelid reconstruction. The residual tarsal plate was used as a tarsoconjunctival advancement flap to reconstruct the posterior lamella of the defect. Skin from the posterior aspect of the left ear was grafted onto the reconstructed posterior lamella with two setting tarsorrhaphy sutures. One month postoperatively, the patient had an excellent cosmetic result with appropriate upper eyelid height and curvature, although cilia were not transplanted. The technique described offers a one-stage procedure with a simple surgical method providing on appropriate cosmetic and functional result.Sameh Saad, Yasuhiro Takahashi, Lucy A. Goold and Hirohiko Kakizak