Ipilimumab deemed safe for autoimmune disease patients, with close monitoring

Last Updated: 2015-12-09

By Anne Harding

NEW YORK (Reuters Health) - Melanoma patients with preexisting autoimmune disease can be safely treated with ipilimumab, as long as they are monitored carefully, according to a new review of 30 cases.

"Overall in this group of patients with autoimmune disease, ipilimumab seems to be safe," said Dr. Douglas B. Johnson of Vanderbilt University in Nashville, who has consulted for Bristol-Myers Squibb, which markets ipilimumab as Yervoy.

"The patient should definitely be watched closely and counseled to alert the doctor if they are having any worsening of the autoimmune disease or any of the standard side effects of these drugs," he told Reuters Health.

Clinical trials of ipilimumab largely excluded people with autoimmune disease, due to concerns about immune-related adverse events, Dr. Johnson and colleagues note in their report, published online December 3 in JAMA Oncology.

To better understand the safety and efficacy of ipilimumab in patients with autoimmune disease, the team looked at 30 patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab. Patients came from nine different tertiary referral centers. Six had rheumatoid arthritis, five had psoriasis, six had inflammatory bowel disease, two had lupus, two had multiple sclerosis, two had autoimmune thyroiditis, and seven had other autoimmune conditions.

Thirteen of the patients were taking immunosuppressive therapy when they began taking ipilimumab, usually low-dose prednisone or hydroxychloroquine. Eight of the patients had a worsening of their autoimmune condition with ipilimumab therapy, all of whom were managed with corticosteroids.

Ten patients had conventional immune-related adverse events, two of whom were treated successfully with corticosteroids or infliximab. A patient who had psoriasis at baseline developed immune-related colitis and died, after delaying reporting of symptoms for a week, according to the researchers.

Fifteen of the patients had no flare-up of their autoimmune disease and no immune-related adverse events, while six had an objective response to ipilimumab and one had a durable complete response.

The current report is the largest series of patients with autoimmune disease who received ipilimumab treatment, Dr. Johnson and his colleagues note.

Two newer immune checkpoint inhibitors, the PD-1 inhibitors nivolumab and pembrolizumab, have been introduced to treat melanoma, and are becoming first-line therapies, Dr. Johnson noted.

"The immune therapies are the main treatment options for many patients with melanoma, so really if we're concerned about a patient's underlying autoimmune disease and we don't give them these treatments they essentially have no available treatment options in many cases," he said.

None of the patients in the study had severe, disabling autoimmune disease, Dr. Johnson said, so it's still not clear whether ipilimumab would be safe for these patients. Nevertheless, he added, "this study does address the vast majority of patients with autoimmune diseases."

In an editor's note, Dr. Mary Disis notes that "immune checkpoint inhibitor agents are associated with unique immune-related toxic effects that often make practicing oncologists hesitant to use the drugs."

The new findings, she writes, "underscore the safety of administering ipilimumab in patients with autoimmune disease."

The study was funded by the National Institutes of Health. Several authors reported financial ties to Bristol-Myers Squibb.

SOURCE: http://bit.ly/1Y12bi7 and http://bit.ly/1Qv1ixt

JAMA Oncol 2015.