Rheumatoid Arthritis Is No Bar to Cancer Immunotherapy

ATLANTA -- Disease flares were common in rheumatoid arthritis (RA) patients receiving checkpoint inhibitors for comorbid cancers, a researcher said here, but most patients were able to continue to receive the immunotherapies.

Among 22 RA patients treated with checkpoint inhibitors including ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) -- 12 developed RA exacerbations after starting the immunotherapy, said Sabina Sandigursky, MD, of New York University in New York City. She noted that the 22 patients in the study are the largest such cohort yet assembled.

RA flares prompted only two patients to permanently discontinue immunotherapy and one took a temporary holiday; one other patient discontinued because of other immune-related effects. The rest continued on therapy uninterrupted, she said at the American College of Rheumatology annual meeting.

Median overall survival in the cohort was 10.5 months; the study did not include details of patients' cancers such as stage, performance status, or prior therapies.

Sandigursky said the important take-home message is that RA is by no means a contraindication to checkpoint inhibitor therapy. In patients with RA or other rheumatic diseases, she suggested that their oncologists should work with rheumatologists to optimize management of toxicities associated with immunotherapies.

Checkpoint inhibitors include drugs targeting CTLA-4 (ipilimumab), PD-1 (nivolumab, pembrolizumab), and PD-L1 (e.g., atezolizumab [Tecentriq] and avelumab [Bavencio], although none of the current cohort received these) molecules. Some cancer cells exploit these molecules to dial down immune attacks that would otherwise kill them; the checkpoint inhibitors restore the immune activity, producing a highly potent anti-cancer effect, particularly in melanoma and some lung cancers.

However, with this effect comes activation of overall immune activity that may develop into inflammatory and/or autoimmune symptoms. Nivolumab's label, for example, warns of seven possible immune-mediated side effects involving the liver, colon, skin, and other organs.

Naturally, that has prompted concern that patients with pre-existing autoimmune diseases may see their conditions worsen with checkpoint inhibitors. But no data were collected in the drugs' clinical trials because such patients were excluded, Sandigursky said.

That leaves it to researchers such as herself to look for patients with autoimmune diseases and comorbid cancers who are receiving the drugs as part of their real-world care.

The 22-patient cohort was about age 67 on average and, as is typical of RA, three-quarters were women. RA was inactive when starting immunotherapy in all but three cases. Six patients were taking no medications for their RA; among the rest, 12 were taking corticosteroids and seven were on methotrexate. Smaller numbers were taking other traditional disease-modifying antirheumatic drugs (DMARDs) or intravenous immune globulins. Only one patient in the cohort was taking a biologic drug (etanercept [Enbrel]) when immunotherapy began.

Normally, among 22 RA patients in their 60s and 70s, many more would be on biologics. Sandigursky told MedPage Today that RA treatment was likely scaled back before starting on immunotherapy (perhaps long before, given that patients may have received immunosuppressing chemotherapies as first-line treatment for their cancers).

After starting immunotherapy, 15 patients developed no immune-related adverse effects (not counting RA flares); four had dermatitis, and three cases of colitis and one of hepatitis were seen. Median times to onset of these symptoms were 1 to 3 months. None were grade 4 and two were grade 3. Sandigursky said they were managed successfully with systemic or topical steroids.

Flares, too, were manageable, she said. Two patients got NSAIDs only. The other 10, Sandigursky said, "were adequately managed with oral prednisone," with two also receiving DMARDs.