From the Journals

Checkpoint inhibitors look safe in rheumatology patients


 

FROM ARTHRITIS AND RHEUMATOLOGY

People with rheumatologic diseases and cancer appear to be at no higher risk of having an adverse event or disease flare if they receive checkpoint inhibitor therapy, compared with the general population, experience from the Mayo Clinic suggests.

In a brief report published in Arthritis and Rheumatology, a team from the Mayo Clinic in Rochester, Minn., reported on 16 patients with rheumatologic diseases who received cancer immunotherapy. They found that only a minority experienced a flare of their disease or another immune-related event.

The rate of severe immune-related adverse effects (IRAEs) with a single immune checkpoint inhibitor (ICI) has been reported to be less than 2% among the average population. However, less is known about patients with underlying rheumatologic disease, largely because initial trials of ICIs had excluded patients with autoimmune diseases for fear the treatment would induce a disease flare, the researchers noted.

Small studies have suggested that people with inflammatory arthritis or connective tissue diseases have higher rates of IRAEs with immunotherapy, but it is unclear how often these events represented flares of their disease or new autoimmune events, and whether the events had any predictive significance for cancer survival.

In this study, researchers performed a retrospective review of medical records and identified 16 patients with rheumatologic diseases who had received checkpoint inhibitor therapy at the Mayo Clinic between 2011 and 2016.

The most common rheumatologic diseases among the 16 patients were rheumatoid arthritis, polymyalgia rheumatica, Sjögren’s syndrome, and systemic lupus erythematosus, and the most common cancers were malignant melanoma, pulmonary malignancies, and non-Hodgkin lymphoma. Seven of the patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatologic disease upon initiation of a checkpoint inhibitor.

Ten patients had received a prior disease-modifying antirheumatic drug, but only two patients were still taking this at the time of ICI initiation.

Results showed that six of the patients (38%) had an IRAE or flare of their rheumatologic disease, two were graded as mild. All of the patients responded well to glucocorticoids and discontinuation of therapy. The most common event was colitis and just one patient had a flare of rheumatologic disease.

“This is consistent with what is currently known about the management of IRAEs,” the research team wrote. “This study adds further support to the emerging notion that the rate of IRAEs is not necessarily higher in this group compared to the general population.”

The type and severity of rheumatologic disease may play an important role in both the risk of disease flare and IRAEs, a factor that they were unable to assess in the current study, the researchers wrote.

“Further large, prospective studies are needed to address the link between the type, severity, and concurrent rheumatologic disease activity on the risk of flare and IRAE. It is possible that patients with more severe or active disease are at higher risk for these complications,” they wrote.

While patients in the study did not appear to have significantly increased incidence or severity of adverse effects, the research team advised that “treatment decisions must factor in clinical judgement.”

They noted that some studies had proposed predictive biomarkers, pretreatment workup, and monitoring, but this advice was based on a small body of evidence.

“Larger, prospective studies will be necessary to validate these findings and establish evidence-based guidelines for appropriate identification and rating of the rheumatologic IRAEs as well as their treatment, such that patients can continue to receive potentially life-saving cancer treatments,” they wrote.

One of the researchers reported advisory board membership with Bristol-Myers Squibb.

SOURCE: Richter M et al. Arthritis Rheumatol. 2018 Jan 24. doi: 10.1002/art.40397.

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