1510P - Delayed onset immune related adverse effects (IRAEs) of pembrolizumab in non-small cell lung cancer

Abstract

BackgroundThe humanised PD1 antibody, Pembrolizumab, is used as monotherapy in the 1st and 2nd line setting for patients with advanced non-small cell lung cancer (NSCLC). There is a lack of data about the delayed onset of IRAEs which is important as patients can be on prolonged treatment. MethodsThis is a retrospective study of NSCLC patients treated with pembrolizumab across 4 institutions in London (North Middlesex University Hospital, Princess Alexandra Hospital, St. Bartholomew’s Hospital and University College London Hospital). IRAEs recorded on clinic letters from start of treatment until March 2019 were categorised as early (<180 days from first dose) or delayed (>180 days). Results139 patients (60% male) with advanced NSCLC were treated with pembrolizumab. Median age was 67 years and 75% (104/139) were adenocarcinoma. Median follow up was 191 days with 3 patients completing 2 years of treatment. IRAEs were reported in 53% (73/139) with patients experiencing up to five different IRAEs. 34% (40/116) of all IRAEs were delayed and colitis was the most common (54%) late IRAE, followed by skin & mucosal toxicities (Table). There were no differences in the grade of severity (P=0.37) or number of toxicities requiring permanent discontinuation of pembrolizumab between early and delayed IRAEs (P=0.31). All patients with pneumonitis, 88% with hepatitis and 87% with colitis were treated with steroids. In 88% (35/40) of patients with delayed IRAEs, toxicities resolved or became asymptomatic. All but 2 cases of endocrinopathy required chronic hormone replacement therapy. 19 cases of treating through toxicity with maintenance low dose corticosteroid were identified. Of these, only one developed progressive disease with the remainder continuing to receive pembrolizumab.Table1510PTableIRAEsEarlyDelayedGeneral e.g. Fatigue172Rash/Pruritis2311Colitis1112Hypo/Hyperthyroidism73Hepatitis53Pneumonitis53Hypophysitis22Arthritis13Blepharitis/Conjunctivitis31Polymyalgia/Myositis21Nephritis01TOTAL76 (66%)40 (34%) ConclusionsDelayed onset IRAEs are common and exhibit a different profile of toxicities compared to early onset. They are no more severe than early IRAEs and can be effectively managed to allow patients to continue their treatment. Legal entity responsible for the studyNorth Middlesex University Hospital, Princess Alexandra Hospital, St. Bartholomew’s Hospital and University College London Hospital. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.