LAUSR

Background Immune checkpoint therapy is a major advance in the field of oncology. Agents targeting CTLA-4, programmed cell death protein 1 (PD-1) and PD-ligand 1 have produced significant survival benefits in patients with malignancies. With these therapies have come a unique spectrum of adverse events related to over-activation of the immune system with resultant autoimmune disease. To date reports of rheumatic immune related AEs (irAEs) have not been adequately characterized, as they are infrequently reported in clinical trials. We describe the largest series of rheumatic irAEs secondary to checkpoint inhibitors to date. Objectives To report our 22 month experience with 19 patients evaluated in the Cleveland Clinic Rheumatology department. Methods A retrospective chart review was performed on 19 patients, 16 without pre-existing autoimmune disease (AID) and 3 with pre-existing AID, seen in our rheumatology department February 2015-December 2016. 2 designated rheumatologists evaluated all patients. Recorded information included gender, age, age at malignancy diagnosis, malignancy details, checkpoint inhibitor, nature of rheumatic irAE, time of onset, diagnostic data, treatment of irAE and response to treatment. Results In the group without pre-existing AID 56% developed a rheumatic irAE within 16 weeks of starting immunotherapy, with median time to onset of 14.5 weeks (table 1). Of the 3 patients with pre-existing AID, 1 experienced a disease flare after starting immunotherapy.Table 1. Demographic features, cancer types, immunotherapy and rheumatic irAEs Patient Age Sex Malignancy Immunotherapy irAE Serology Time to onset (weeks) Treatment Improvement Immunotherapy held for irAE 1 74 F NSCL Nivo Arthritis ANA 1:160 7.3 Prednisone 40 mg Significant Y Anti-dsDNA 77 2 49 F Melanoma Ipi Arthritis 52.7 Prednisone 20 mg Moderate Y Pembrolizumab HCQ 3 42 F RCC Ipi/Nivo Arthritis 3 Prednisone Moderate N Infliximab, MTX Etanercept 4 57 M RCC Ipi/Nivo Arthritis RF 214 48.4 Prednisone, MTX Significant N Etanercept Adalimumab 5 59 F Melanoma Ipi/Nivo Arthritis 21.7 Prednisone 60 mg Minimal N 6 81 M Melanoma Ipi/Nivo Arthritis ANA 1.5 13.1 Prednisone 15 mg Moderate Y 7 59 M RCC Ipi/Nivo Arthritis ANA 1.8 56 Prednisone 10 mg Minimal N 8 53 M Melanoma Ipi/Nivo Arthritis 16 Methylprednisolone 80 mg IM Minimal Y 9 63 59 NSCL Nivo Arthritis ANA 1:160 38 Prednisone 30 mg Minimal Y Methorexate 10 57 F Melanoma Ipi/Nivo Arthritis ANA 1:320 6.7 Prednisone 30 mg Significant Y Sicca 6.7 11 61 M Melanoma Ipi/Nivo Sicca 5.3 Prednisone 60 mg* Significant Y^ 12 63 M RCC Atezolizumab Sicca 21.9 Prednisone 60 mg* Significant Y^ 13 68 M Melanoma Ipi/Nivo Sicca ANA 1:1280 8.1 Prednisone 30 mg Significant Y PMR SSA 14 79 M Melanoma Nivo PMR 2 Prednisone 20 mg Moderate Y Sicca 15 63 M RCC Nivo PMR 213 Prednisone 40 mg Moderate Y Infliximab Tocilizumab 16 68 M NSCL Tremelimumab Myositis 4.6 IV methylpred 60 mg Moderate Y Durvalumab Prednisone 60 mg NSCL non-small cell lung cancer, RCC renal cell carcinoma, Ipi ipilimumab, Nivo nivolimumab, RF rheumatoid factor HCQ hydroxychloroquine, MTX methotrexate, *Prednisone given for hypophysitis. ^Immunotherapy held for hypophysitis. Conclusions Rheumatic irAEs is a new field that will continue to grow. At this stage we have more questions than answers regarding their epidemiology, natural history and pathophysiology. Our findings reinforce that rheumatic irAEs are complex, at times require aggressive immunosuppression and can impact checkpoint inhibitor therapy for the underlying malignancy. Disclosure of Interest C. Calabrese: None declared, E. Kirchner: None declared, A. Kontzias: None declared, V. Velcheti Grant/research support from: Genentech, Bristol-Myers Squibb, Merck, Astra Zeneca, Genoptix, Consultant for: Genentech, Bristol-Myers Squibb, Merck, Astra Zeneca, Celgene, Genoptix, Foundation Medicine, L. Calabrese Consultant for: Bristol-Myers Squibb