816 Selective immune suppression using interleukin-6 blockade in immune related adverse events

Background Managing immune-related adverse events (irAEs) has become a critical challenge with the increasing implementation of immune-checkpoint inhibitors (ICIs) in cancer treatment. IrAEs may cause treatment interruption or discontinuation, rate which is higher multi-agent ICI regimen needed to overcome resistant tumor microenvironment. Herein, we describe our clinical experience using interleukin-6 receptor antagonists (IL-6RA) manage irAEs patients receiving ICIs. Methods We conducted retrospective, multi-center study evaluate safety and efficacy IL-6RA for irAE management. Eligible were identified from institutional databases (pharmacy records, registries, oncology specialty clinic records diagnosis management irAEs). The primary objective was assessing changes symptoms. secondary overall response (ORR) before after Results A total 81 received an (tocilizumab sarilumab); median age 66 years, 41% females, 70% single-agent anti-PD-1 23% nivolumab plus ipilimumab. Cancer types primarily melanoma (44%), genitourinary (37%), lung (8.6%). Indications inflammatory arthritis (74%), polymyalgia rheumatica (6%), myositis/myocarditis/myasthenia gravis (5%) encephalitis (5%), 1% each pneumonitis, colitis, hepatitis, central nervous system vasculitis, oral mucositis, flare pre-existing myasthenia gravis, psoriasis, Crohn's disease. Notably, 83 % corticosteroids as first-line therapy, 29% disease-modifying antirheumatic drugs, without improvement. After initiation IL-6RA, improvement observed 78% 2.1 months. Of evaluable arthritis, disease activity index (CDAI) at 28, indicating high activity, dropped 6 treatment, low activity. CRP level 59.5 mg/L 1.5 within 10 weeks Seventy-two tolerated nine stopped due side effects. Thirty-eight evaluated by RECIST 1.1 criteria; ORR 58% prior 66% 21 patients, 62% compared 71% (figure 1). Conclusions Our demonstrated that targeting IL-6R could be effective approach mitigate autoimmunity while maintaining possibly boosting immunity. Clinical trials are currently evaluating tocilizumab combination ICIs melanoma, non-small cell cancer, urothelial carcinoma ( NCT04940299 , NCT03999749 ). Ethics Approval approved University Texas MD Anderson Center intuition's Board, approval number PA19-0089 Abstract 816 Figure 1 patient sinonasal malignant involving ethmoid air cells. (A) Baseline maximum intensity projection (MIP) PET image month (ipilimumab nivolumab) shows avid FDG uptake cells (arrow). (B) MIP 7 months resolution site tumor, consistent complete response. (C) Concurrent corresponding fused PET-CT images show radiotracer knee joints, suggestive arthritis. (D) concomitant therapy IL6R antagonist persistent absence hypermetabolic paranasal sinuses, (E) physiologic resolving