Cancer treatment with checkpoint inhibitors in RA patients?

Even though about half of the patients experienced a flare of their rheumatoid arthritis (RA), cancer therapy with immune checkpoint inhibitors (ICI) can be continued in most of the cases [1]. Results indicate that rates for serious immune-related adverse events are comparable to those for patients lacking autoimmune disease.

Having comorbidity of autoimmune disease generally leads to the exclusion of oncologic trials with ICI, as there are worries about more immune-related adverse events (irAEs) [1]. “However, patients with autoimmune diseases have the potential to benefit from the use of these therapies,” commented Dr Sabina Sandigursky (New York University Langone Medical Center, USA).

The reported study investigated 84 patients with known autoimmunity who had been treated with anti-CTLA-4 and PD-1 for their cancer from 2011-2018. There were 22 patients of this group who suffered from RA. The majority was female (73%), median age was 67. When starting ICI, 73% of the patients were on immunomodulatory treatment, including 36% taking corticosteroids and 32% methotrexate. With regard to cancer subtypes, 32% each were diagnosed with melanoma or non-small cell lung cancer. Primary trial endpoints were incidences of irAEs and RA flares.

IrAEs occurred in 32% of the RA patients, but only 9% were of severe nature. RA flares were observed in 55% of patients, and ICI treatment had to be entirely stopped in 1 patient; short-term discontinuation was necessary in 23%. Depending on the drug that was administered, the rate of serious irAEs in patients without autoimmunity ranged from 7-30%. Flare treatment was performed with corticosteroids in 75% of the cases. In general, toxicity occurred in 32% of patients, the most frequent being dermatitis (18%) and colitis (14%). The overall survival for RA patients under ICI was 10.5 months after ICI initiation.

“Our data suggests that patients with RA may be treated with immunotherapy and attain rates of response that are similar to the general population with a 50% flare rate,” said Dr Sandigursky. “If validated in prospective clinical trials, this study’s findings may open new treatment options for patients with autoimmune diseases and concurrent malignancy. A co-management approach between the oncologist and rheumatologist can help recognise and treat immunotherapy-related toxicities if they do arise.” Rheumatologists and oncologists have reached an interesting therapeutic crossroad and need to consider the impact of RA-directed therapy on overall tumour survival, as steroids and disease-modifying antirheumatic drugs (DMARDs) might impact anti-tumoral immunity [2].

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   1. Efuni E, et al. Abstract 1339. ACR 2019. 8-13 November, Atlanta (GA/USA).
   2. McGonagle D, et al. Autoimmun Rev. 2019 Dec 12:102456.

Posted on 4 February, 202018 March, 2021