BI02 Severe photosensitivity complicating anti-PDL1 checkpoint inhibitor treatment: an emerging immunotherapy-related skin toxicity
Authors: Patel Majeeda , Cernova Jeva , Harwood Catherine 
Published: June 2024

Abstract
Cutaneous adverse events with immune checkpoint inhibitors (ICI) are common and their spectrum is ever expanding. We describe the first case of photosensitivity associated with the anti-programmed death ligand (PDL)1 inhibitor durvalumab for transitional cell carcinoma (TCC) of the bladder, which recurred with subsequent use of the anti-PDL1 inhibitor avelumab. A 73-year-old South Asian male patient developed an intensely itchy photosensitive rash. He had a completely resected bladder TCC and was recruited to a clinical trial for residual TCC in situ and randomized to durvalumab infusions (with intravesical bacille Calmette–Guérin). The rash developed after the second infusion; its severity required oral prednisolone 1 mg kg−1 per day started by oncology. He had a lichenoid and profoundly hyperpigmented rash affecting his face, neck, hands and feet with no other clinical features of dermatomyositis. Skin biopsy demonstrated a lichenoid/interface dermatitis. Serum creatinine kinase was normal and an autoimmune screen, extended myositis panel and porphyria screen were negative. There was no clinical or radiological evidence of TCC in situ progression or other malignancy. Patch testing and phototesting were unavailable due to the COVID-19 pandemic. Durvalumab was stopped as the patient had TCC in situ only. The rash cleared with topical steroids and photoprotection. Over the following 3 years the patient had no further rashes. However, in August 2022, the TCC in situ progressed to metastatic TCC. After a course of cisplatin and gemcitabine chemotherapy, maintenance avelumab was started in May 2023. In August 2023 the patient developed rapid recurrence of the photosensitive rash after a prolonged episode of intense sun exposure through a car window without photoprotection. Skin biopsy again demonstrated an interface dermatitis with negative direct immunofluorescence. Repeat autoimmune, creatine kinase and porphyrin screens were negative. Topical steroids and strict photoprotection have enabled the patient to continue with avelumab for metastatic TCC. Photosensitivity in the context of malignancy may be a manifestation of paraneoplastic conditions such as dermatomyositis. However, associations with systemic anticancer therapies are increasingly being recognized. This is well established for selected targeted therapies including BRAF, epidermal growth factor receptor and Janus kinase inhibitors (e.g. vemurafenib, erlotinib, ruxolitinib) and in some the mechanism responsible is linked to second skin malignancies. There have been three reports of photosensitivity with anti-PD1 ICIs in recent years but, to our knowledge, this is the first report with anti-PDL1 ICIs. Whether this will also lead to second skin malignancies may become apparent with time. Finally, this case demonstrates the importance of recognizing new or rare cutaneous toxicities with anticancer treatments and their appropriate management in order to allow their continuation where possible, which is the ultimate goal of supportive dermato - oncology.