Good news for melanoma patients with rheumatic toxicities

Rheumatoid side-effects of advanced melanoma treatment with immune checkpoint inhibitors predict good outcomes and can be safely treated.

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Cancer patients who have new or worsening rheumatic side-effects after treatment with an immune checkpoint inhibitor tend to have a better response to their cancer treatment, according to Australian research presented at the American College of Rheumatology conference in Philadelphia.  

The Macquarie University study showed that rheumatic side effects and thyroiditis were predictors of favourable tumour response even when controlling for other predictors of tumour response such as age, gender, whether the patient had immunosuppression during treatment, a pre-existing autoimmune disease, other organ-related side-effects like colitis thyroiditis, and also what tumour they had. 

“It means that we can say to cancer patients referred to [rheumatologists] with anything from a mild exacerbation of their osteoarthritis to more severe new onset inflammatory arthritis, that they’re more likely to have a good tumour response to their treatment,” rheumatologist and lead author Dr Alana Bruce told The Medical Republic.

“And treating them [for their rheumatic conditions] with immunosuppression is unlikely to have an effect on their response to cancer treatment.”

The study involved 147 people with stage III or IV melanoma who were being treated with immune checkpoint inhibitors. In their clinical notes, around 40% had clinician-documented arthralgia, 5% had inflammatory arthritis and 3% had a polymyalgia rheumatica-like syndrome. In the survey filled out by each participant, 32% reported that they had new peripheral joint, spinal or muscle symptoms and 21% had exacerbations. All participants were followed up for 12 months.  

“We had two models – one using the patient reported rheumatic toxicities, the other using clinician reported rheumatic toxicities. And we found that patient reported rheumatic toxicities [OR=14] and thyroiditis [OR=12] were predictors of tumour responses, but clinician recorded toxicities were not,” Dr Bruce said. 

In both models, it was found that having immunosuppression to counter rheumatic toxicity did not negatively predict tumour response. 

Overall, 87% of patients (128 patients out of 147) responded to cancer treatment, but the rate was higher for those with clinician-documented rheumatic disease (94% vs 78%). Tumour response was complete in 31% of patients, partial in 30%, 6% had stable disease and 19% were disease free (where the melanoma was removed and the patient was still treated with a checkpoint inhibitor). 

Because patients with advanced melanoma tend to be older, around 67% have pre-existing rheumatic conditions like osteoarthritis of back pain, said Dr Bruce. “And we found that being symptomatic prior to getting checkpoint inhibitor therapy was the best predictor of developing rheumatic side effects during therapy. Those patients were over three times more likely to develop side effects that were new or worsening rheumatic symptoms during treatment, according to the survey data.” 

Exacerbations and new rheumatic conditions are common during and after treatment for advanced melanoma with an immune checkpoint inhibitor, said Dr Bruce, and referring cancer patients early to a rheumatologist would help ameliorate symptoms and reduce the likelihood of needing to stop treatment due to toxicity. 

“Around 70% of patients in the study had metastatic disease. Our aim is to enable them to have the treatment they require and to support them so they can continue to have a good quality of life while undergoing treatment,” Dr Bruce said. 

“In the end, the name of the game is to support the oncologist and to support the patient to get their treatment.”