Background/Purpose: During the past decade, antibody-based immunotherapies (including anti-PD1, anti-PD-L1, and anti-CTLA4) have revolutionized cancer treatment by enhancing the body’s immune response against tumors. However, it is not possible to specifically target the inhibition signals in the tumor microenvironment (TME) without affecting other areas. Blocking these inhibitory checkpoints can cause autoimmune-like phenomena called immune-related side effects  in multiple organ systems due to global immune activation. Therefore, the use of ICI in patients with pre-existing autoimmune diseases (PADs) has been hampered by the potential for immune-related adverse events (irAEs). Rheumatic irAEs encompass inflammatory arthritis, sicca syndrome, myositis, polymyalgia rheumatica, and several other rare phenotypes. The CTLA-4 and PD-1/PD-L1 pathways have been linked to the pathophysiology of rheumatoid arthritis (RA). In this study, we particularly focused on the outcome of ICI treatment in patients with pre-existing RA.

Methods: We searched PubMed from 2014 to 2024 using the keywords “ICI, irAEs, rheumatoid arthritis, rheumatology”. We only included studies that involved patients with rheumatoid arthritis and we found a total of 23 studies. Data on RA disease activity and treatment regimens were collected, including the use of systemic steroids, DMARDs, and symptomatic treatments.

Results: We identified 1616 oncology patients with PAD who were given ICIs. The mean age of the participants ranged from 54 to 72. The most common cancer types were melanoma, NSCLC, and urinary tract carcinomas. 194 out of 1616 patients (12%) had rheumatoid arthritis diagnosis according to ACR/EULAR criteria. Among the reported ones, only 41.9% (95% CI 32.5%, 51.3%) of RA patients showed disease activity. Treatment for pre-existing RA varied, with 19% treated with only systemic steroids, 8% with steroids and DMARDs, 14% with only DMARDs, and 58% with only symptomatic treatment. 25.3% (95% CI 18.5%, 32.1%) of patients developed irAEs (colitis mostly), while 50% (95% CI 42.2%, 57.8%) had a flare of their pre-existing autoimmune diseases. The ICI discontinuation rate due to irAEs or flares was 15.9% (95% CI 8.9%, 22.8%). Only one patient’s death was thought to be due to irAEs (colitis); other deaths were attributed to progressive disease. De novo irAEs and flares were effectively managed using standard treatment protocols in almost all cases and did not prevent the patients from receiving clinical benefits.

Conclusion: Our research discovered that more than 70% of cancer patients with pre-existing autoimmune diseases experienced either autoimmune exacerbations or immune-related adverse events. Immunotherapy for cancer presents ongoing challenges in individuals with rheumatic diseases. Pre-existing autoimmunity does not serve as an absolute contraindication for ICI treatment. It is crucial to engage in a thorough discussion regarding individual expectations and available treatment options. There is very limited data on this topic, highlighting the need for further research to guide clinical decision-making.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/can-immune-checkpoint-inhibitors-safely-combat-cancer-in-patients-with-rheumatoid-arthritis/