FRI0590\u2005UVEITIS SECONDARY TO CHECKPOINT INHIBITORS

Abstract

Background The introduction of immunotherapy (immune checkpoint inhibitors, ICI) has led to a revolution in oncological treatments. The inhibitors of CTLA4 (ipilimumab), of PD1 (pembrolizumab, nivolumab) and of the ligand of PD1 (atezolizumab, avelumab, durvalumab) regulate T activation and its effector function, being effective for the treatment of various types of cancer1. However, this effect leads to a series of immune-mediated adverse events, among which uveitis of autoimmune mechanism have been described in about 1% of treatments2. Objectives Methods: descriptive study of retrospective review of the cases of a tertiary hospital with about 1000 treatments between the beginning of 2014 and the end of 2018. Results A series of 4 cases of uveitis of autoimmune origin associated with ICI is presented (see table). The series described has characteristics similar to the information previously reported in the literature2, with an incidence of around 0.4%, according to the previously described, with frequencies of ocular toxicity around 1%, being the uveitis is the most frequent form of presentation. The time of presentation of uveitis since the beginning of treatment has been in all cases in the first 6 months. The forms of presentation described before, ranges from anterior uveitis (AU) to panuveitis and often papilledema, usually bilateral, as are all those described in our series. In addition, 50% are AU (grade 2) and the other 50% panuveitis with papilledema (grade 3). In all the cases described, treatment was interrupted, a half it could be reintroduced without recurrence of uveitis. All the patients received topical treatment, the more severe systemic corticosteroids at doses of 0.5-1 mg/kg in accordance with the recommendations. The final prognosis was good, with preservation of VA in all cases, and topical and systemic treatment could be withdrawn in all patients. A patient treated with Ipilimumab presented synechiae as a complication. ONCO diagnosis ONCO treatment time OPH diagnosis Toxicity (G) OPH tretament ICI withdrawal Prognosis Other toxicities ♂ 79 Melanoma BRAF wt+ retroperitonealmtt Pembrolizumab x7Ipilimumab x2 6m6w Bilateral AU with synechia 2 Prednisone 1 mg/kg+Topical Temporal No inflammation without treatmentVA PreservedSynechia Transaminitis G2Asthenia G2 ♂ 85 Cáncer de vejiga localizado avanzado Atelizumab x7 5m Bilateral AU 2 Topical Definitive No inflammation without treatmentVA Preserved PMR G2Thyroiditis G1Transaminitis G1Mucositis G1 ♂ 45 Melanoma BRAF mutant (retropectoral mass) Pembrolizumab x5 4m Bilateral Panuveitis with synechia+ papilledema 3 Prednisone 0,5 mg/kg+ topical Definitive No inflammation without treatamentVA Preserved None ♂ 47 Melanoma BRAF wt (abdomial mass+peritoneal mtt+ adrenal mtt) Nivolumab x2Ipilimumab x1 2m1m Bilateral Panuveitis with synechia+ papilledema 3 Prednisone 0,5 mg/kg+ topical Nivolumab temporalIpilimumab definitive No inflammation without treatamentVA Preserved Rash G1Pruritus G1Vitíligo Conclusion Uveitis is an infrequent, although potentially serious, immune-mediated side effect of ICI. Early recognition, discarding other causes of uveitis, particularly the masquerade syndrome, and early intervention are key to a good prognosis. The collaboration between the oncology teams and the ocular inflammation units must be close to establish the correct diagnosis and treatment, as well as to decide individually on the reintroduction or not of the oncological treatment. The implementation of registers on the adverse effects of these drugs can help to dimension the problem more accurately. References [1] Calabrese LH, Calabrese C, Capelli, LC. Rheumatic immune-related adverse events from cancer immunotherapy. Nat Rev Rheumatol. 2018Oct;14(10):569-579. [2] Dalvin LA, Shields CL, Orloff M, Sato T, Shields JA. Checkpoint inhibitor immune therapy: Systemic Indications and Ophthalmic Side Effects. Retina. 2018Jun;38(6):1063-1078. Disclosure of Interests None declared