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Checkpoint Inhibitor Therapy Feasible in Patients with Preexisting Rheumatoid Arthritis Diagnosed with Cancer

Atlanta, GA—Although immunotherapy with checkpoint inhibitors is an important advancement in the treatment of several types of cancer, clinicians have questioned whether patients with preexisting autoimmune disorders, such as rheumatoid arthritis (RA), can be safely treated with these agents. Results from a small, retrospective study, presented at the 2019 American College of Rheumatology Annual Meeting, suggest that they can.

“Having preexisting RA is not an absolute contraindication for checkpoint inhibitor therapy. Patients should be treated with caution because they may flare, which can’t be predicted. Checkpoint inhibitor therapy may be given to RA patients with concomitant malignancy as they stand to benefit from immunotherapy,” stated the lead investigator Sabina Sandigursky, MD, Instructor, Department of Medicine, NYU Langone Medical Center, New York City.

Study Details

Dr Sandigursky and colleagues conducted a retrospective analysis of 84 patients with autoimmune disorders who were diagnosed with cancer that was amenable to treatment with checkpoint inhibitors; 22 were identified as having RA. Median age was 67 years and 73% of patients were female. Nineteen patients (86%) had inactive RA, and 3 (14%) had active RA. Of the 3 patients with active RA, 1 patient was receiving a bDMARD. Sixteen patients were receiving immunomodulatory therapy for RA at the start of checkpoint inhibitor treatment. Cancer types were predominately melanoma (N = 7), lung (including adenocarcinoma (N = 4), and squamous-cell carcinoma (N = 3). Other cancer types included Merkel-cell carcinoma, ovarian cancer, head and neck cancer, renal cancer, bladder cancer, and Hodgkin lymphoma.

Four patients received ipilimumab, 9 received nivolumab, and 13 received pembrolizumab. Some patients were switched from one agent to another during the trial. One patient received combination checkpoint inhibitor therapy with ipilimumab and nivolumab followed by monotherapy with pembrolizumab; 2 patients received sequential therapy with ipilimumab and either nivolumab or pembrolizumab; and 1 patient received monotherapy with nivolumab and subsequently was switched to pembrolizumab.

New immune-related adverse events developed in 7 (32%) patients, with the most common toxicities being dermatitis (N = 4) and colitis (N = 3). Most of these events were grades 1 or 2; there were 2 patients who experienced a grade 3 event, and no patient developed grade 4 or 5 events. Checkpoint inhibitor treatment was temporarily discontinued in 5 patients because of immune-related adverse events, and 1 patient required permanent discontinuation.

The rates of immune-related adverse events were similar to those reported in a general population of patients with cancer who were not diagnosed with RA and who were treated with checkpoint inhibitors, Dr Sandigursky noted.

RA flares were seen in 12 (55%) patients, 9 of whom received oral corticosteroids as treatment for the flare. Checkpoint inhibitor treatment was permanently discontinued in 1 patient because of RA flare.

Overall, an RA flare, immune-related adverse events, or both occurred in 16 (73%) of the 22 patients.

Median overall survival of patients with RA after initiating checkpoint inhibitor treatment was 10.5 months.

“Our data suggest that rates of flare associated with [checkpoint inhibitor] use are approximately 50%. Ongoing clinical trials are evaluating this question prospectively. If our findings are validated, they may pave the way for new treatment options for patients with RA and concurrent malignancy,” Dr Sandigursky commented.

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