Background/Purpose: Immune checkpoint inhibitors (ICI) targeting CTLA-4, such as ipilimumab (anti-CTLA4), or PD-1/PD-L1, such as nivolumab and pembrolizumab are increasingly utilized in a wide variety of malignancies including melanoma, head and neck tumors, and small and non-small cell lung cancers. By upregulating the immune system to prevent evasion and promote destruction of cancer cells, these ICI may cause immune related adverse events (irAEs) which mimic autoimmune diseases such as inflammatory arthritis (RA, SLE, PMR), inflammatory bowel diseases (UC, Crohn’s), and psoriasis. We sought to gain a better understanding of the range of irAEs that occur from ICI use at our institution including the type, severity, timing from onset of therapy, management, and ultimately how these impact patient outcomes. Better understanding of the irAEs provides a unique opportunity to explore and understand the pathogenesis of autoimmune diseases.

Methods: We identified patients who have received ipilimumab, nivolumab and/or pembrolizumab at UNC between January 2004 through July 9, 2017. We investigated the number of patients started on each immunotherapy and for which indication. Through chart review, we further investigated each type and severity of irAEs, their timing, management, duration, management of cancer therapy and cancer response.

Results: Between January 2004 and July 2017, 116 patients received ipilimumab (most frequently for melanoma in 91.3% of patients), 231 patients received pembrolizumab, and 444 patients received nivolumab. Immune related adverse events occurred in 72.4% of patients who received ipilimumab (52.6% of these patients also received nivolumab either in combination or monotherapy). The most frequent irAE was rash (40.5%), colitis (32.8%), thyroid disease (23.3%), musculoskeletal (MSK) (13.8%), hepatitis (12%) and hypophysitis/adrenal insufficiency (12%). The MSK irAEs were mostly asymmetric medium-large joint arthritis, clinically similar to a seronegative spondyloarthritis variant (68.8%) or proximal myalgias similar to PMR. Treatment of the MSK irAEs consisted of NSAIDs, mild to moderate doses of prednisone, intra-articular steroids, colchicine, hydroxychloroquine, apremilast (in a patient with psoriasis), and one patient eventually required knee replacement. Biologics were more frequently utilized in the treatment of severe grade 3-4 colitis with infliximab 5 mg/kg or vedolizumab. Other irAEs less frequently seen were pneumonitis (4.3%), ophthalmologic (4.3%), severe refractory peripheral neuropathy (4.3%), renal (2.3%), pancreatitis (1.7%), and appendicitis (0.9%).

Conclusion: Our findings among patients treated with ipilimumab and nivolumab were in line with prior studies evaluating the irAE secondary to ICIs with skin and GI manifestations being most frequent. In addition, most patients with MSK irAEs had asymmetric medium-large joint involvement mimicking a seronegative spondyloarthropathy. We are currently evaluating other subsets including patients who received nivolumab monotherapy or pembrolizumab.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-related-adverse-events-from-immune-checkpoint-inhibitors-a-retrospective-analysis-from-2004-2017-at-the-university-of-north-carolina-at-chapel-hill/