Background/Purpose: Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape in oncology leading to cures in some cancer types. However, patients with pre-existing autoimmune diseases (AIDs) were largely excluded from ICI trials due to concern for increased toxicity. In clinical practice some patients with rheumatoid arthritis (RA) have been treated with ICIs, but the risks of toxicity and/or disease flare have not been clearly outlined. Here we present data on the safety and efficacy of ICI therapy in patients with RA.

Methods:

We conducted a single institution retrospective analysis to evaluate the safety and efficacy of ICI therapy (anti-CTLA-4 and anti-PD-1) among patients with pre-existing AIDs treated from 2011 to 2018.  Primary endpoints were incidence of immune-related adverse events (irAEs) and AID flares. The secondary endpoint was overall survival (OS). Subgroup analysis for patients with RA was performed with percentages and medians reported.

Results: Of 84 patients with pre-existing autoimmunity who developed malignancy and were treated with ICIs, we identified 22 patients with RA. Sixteen (73%) were female and 6 (27%) male (median age 67).  Most patients had no evidence of active disease 20 (91%) as indicated by their treating physician.  Sixteen (73%) patients were receiving RA immunomodulatory therapy at start of ICI, with 8 (36%) patients receiving systemic corticosteroids and 7 (32%) patients on methotrexate. 

Malignant conditions included 7 (32%) with melanoma, 7 (32%) with non-small cell lung cancer (NSCLC) as well as others. Thirteen patients (59%) were treated with pembrolizumab, 9 (41%) with nivolumab and 4 (18%) received ipilimumab.

IrAEs occurred in 7 (32%) patients with only 2 (9%) developing severe, grade 3 irAEs, a total of 41% developing toxicity of any grade. The most common toxicities were dermatitis 4 (18%) and colitis 3 (14%). ICI was temporarily discontinued due to irAEs in 5 (23%) patients.  Only 1 patient required permanent ICI discontinuation. RA flares occurred in 12 (55%) patients. Most patients 9 (75%) received treatment with oral corticosteroids for RA flare. ICI was permanently discontinued due to flare in only one patient. Overall either flare, irAE or both occurred in 16 (73%) patients. Median OS for patients with RA after start of ICI was 10.5 months.

Conclusion: In our cohort, approximately half of the RA patients experienced flare and fewer had an irAE after initiation of ICI compared to a rate of 5-60% for any grade irAEs and 7-30% in severe irAEs in patients without autoimmune diseases depending on agent used. Most symptoms were manageable and a minority of patients required discontinuation of cancer-directed therapy. While this is a small cohort, the results of this analysis suggest that patients with RA experience severe irAEs at a rate similar to the population without autoimmune diseases. Further study is warranted to determine if ICIs may be offered to patients with RA as first line agents when used for an FDA approved indication. The choice of ICI and its effect on OS in this population also requires further prospective investigation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-immunotherapy-related-toxicity-in-patients-with-rheumatoid-arthritis/