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Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders (AD) or major toxicity with ipilimumab (IPI).
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2016
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Anti-pd-1 TherapyImmunologyImmunoeditingImmunotherapeuticsDermatologyImmunotherapyPd1 StartTumor ImmunologyMetronomic TherapyTumor ImmunityClinical TrialsAutoantibodiesRadiation OncologyMajor ToxicityCancer ResearchHealth SciencesAutoimmune DiseaseMedicineMelanomaImmune SurveillanceAutoimmunityCancer TreatmentAdvanced MelanomaCancer ImmunosurveillancePrior IpiImmune Checkpoint InhibitorImmunosuppressionOncologyIpi Iraes
9515 Background: Anti-PD1-antibodies (PD1) have activity in many cancers, and are standard care for melanoma, lung and renal cancer. All trials excluded patients (pts) with significant preexisting AD or major immune-related adverse events (irAEs) with IPI. We sought to explore the safety and efficacy of PD1 in such pts. Methods: Pts with advanced melanoma and preexisting AD and/or major irAEs with prior IPI (requiring systemic immunosuppression, [IS]) treated with PD1 were retrospectively identified. Data regarding AD, IPI and PD1 treatments, toxicity and outcome were examined. Results: 119 pts were included, 95 with prior IPI. 109 received pembrolizumab, 10 nivolumab. 86 (72%) had ≥ 3 months (mo) follow-up, median (med) 4.6 mo, with med PFS 6.8 mo. 31 (26%) had died. Of 52 pts with preexisting AD, 15 (29%) had active symptoms at PD1 start and 16 (31%) were on IS. The ORR was 33%. 20 (38%) flared with PD1 after a med 1.3 mo, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren’s syndrome, 1/2 with scleroderma, 2/2 with immune thrombocytopaenic purpura, 3/8 with psoriasis, 1/4 with Graves’ disease, 0/6 with gastrointestinal (GI) (including 3 Crohn’s disease) and 0/5 with neurological disorders. 3 (6%) had grade (G) 3 flare, and 2 (4%) discontinued PD1 for flare. 15 (29%) developed other irAEs (5 G3), 3 (6%) discontinued PD1. 67 pts had irAEs requiring IS with prior IPI (9 G2, 51 G3, 7 G4), including 47 with ≥ G3 colitis (15 had infliximab), 2 with G4 hepatitis (1 had antithymocyte globulin), and 9 with hypophysitis. All irAEs except hypophysitis had resolved at PD1 start except in 1 pt (arthritis), 5 were on IS at PD1 start. The ORR was 40%. 2 (3%) had recurrence of IPI irAEs with PD1 (arthritis, colitis), but 23 (34%) developed new irAEs (13, 19% ≥ G3), and 11 (16%) discontinued PD1. There were no treatment related deaths. Conclusions: PD1 have efficacy in pts with preexisting AD and/or major irAEs with IPI. PD1 may flare preexisting AD, particularly rheumatologic, but GI and neurological disorders may flare less. In pts with prior major irAEs with IPI recurrence of the same irAE is rare, but new irAEs occur. The rate of irAEs in these pts appears higher than in clinical trial pts.