Immune Checkpoints Viable in Cancer Patients With RA

Alexander M. Castellino, PhD

November 13, 2019

ATLANTA — Immune checkpoint inhibitors are safe and effective for patients with rheumatoid arthritis who develop malignancies, report investigators.

"In the real world, patients with autoimmune conditions are at a higher risk for malignancies" than people in the general population, said Sabina Sandigursky, MD, from the NYU Langone Medical Center in New York City.

Sabina Sandigursky

"Our study shows that these patients can be successfully treated with immune checkpoint inhibitors and achieve rates of response that are similar to the general population without discontinuing treatment for their RA or their malignancy," she told Medscape Medical News.

Sandigursky and her colleagues conducted a retrospective chart review of 84 patients with autoimmune disorders who developed malignancies. She presented the results here at the American College of Rheumatology 2019 Annual Meeting.

Of the 22 patients with rheumatoid arthritis in this cohort, treating physicians indicated that 19 (86%) had no evidence of active disease. There were seven (32%) cases of melanoma, four (18%) of lung adenocarcinoma, three (14%) of squamous cell lung carcinoma, and eight (36%) of other malignancies.

When immune checkpoint inhibitors were initiated in the 22 patients, 16 (73%) were still receiving immunomodulator therapy for rheumatoid arthritis, which included systemic corticosteroids (55%), hydroxyquinoline (14%), methotrexate (32%), sulfasalazine (9%), and etanercept (5%).

Only one patient was taking a biologic — etanercept — Sandigursky reported, which is typically discontinued when a malignancy is diagnosed and replaced with an immunomodulator to manage the rheumatologic disease.

Patients with RA and other autoimmune diseases are excluded from clinical trials, and our study shows that they can benefit from immune therapies, just as patients in the general population can.

Nine (41%) patients were receiving nivolumab (Opdivo, Bristol-Myers Squibb), 13 (59%) were receiving pembrolizumab (Keytruda, Merck), and five (23%) were receiving ipilimumab (Yervoy, Bristol-Myers Squibb).

Seven patients (32%) experienced immune-related adverse events, but only two (9%) were grade 3 or 4. In addition, four (18%) patients developed dermatitis, three (14%) colitis, and one (5%) hepatitis.

Although most patients had well-controlled rheumatoid arthritis, 12 (55%) experienced flares that had clinical symptoms distinct from the immune-related adverse events.

"It is likely that ICIs activate the immune response, leading to RA flares," Sandigursky explained. "Alternatively, RA flares may arise because treatment for RA was de-escalated in some patients or stopped in others."

This is why it is important to closely monitor these patients for immune-related adverse events, as well as for arthritis flares, she added.

Eight patients received steroids for their rheumatoid arthritis flares, two received a combination of steroids and disease-modifying antirheumatic drugs, and two received nonsteroidal anti-inflammatory drugs.

One patient discontinued immune checkpoint inhibitor therapy because of immune-related adverse events and two discontinued because of flares related to rheumatoid arthritis.

Median overall survival for the 22 patients was 10.1 months, which matches rates in the general population treated with immune checkpoint inhibitors for malignancies, said Sandigursky.

"Patients with RA and other autoimmune diseases are excluded from clinical trials, and our study shows that they can benefit from immune therapies, just as patients in the general population can," she told Medscape Medical News.

When patients with rheumatoid arthritis develop malignancies, Sandigursky said she often gets referrals for a risk–benefit analysis. "A comanagement approach between the oncologist and rheumatologist can help determine if patients with RA are appropriate candidates for ICIs and, working together, they can manage the RA as well as immune-related toxicities should they arise," she explained.

Prospective trials of immune checkpoint inhibitors in patients with autoimmune diseases are needed, she said, noting that the National Cancer Institute has initiated AIM-NIVO, which is being led by Elad Sharon MD, from the National Cancer Institute and Hussein Tawbi, MD, PhD, from the M.D. Anderson Cancer Center in Houston.

AIM-NIVO is a multicenter phase 1b open-label study of nivolumab in patients with cancer and pre-existing autoimmune disease, such as systemic scleroderma, rheumatoid arthritis, irritable bowel disease, and multiple sclerosis.

American College of Rheumatology (ACR) 2019 Annual Meeting: Abstract 1339. Presented November 11, 2019.

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