Immune checkpoint inhibitors tolerable in cancer patients with RA

In cancer patients with rheumatoid arthritis (RA) treated with immune checkpoint inhibitors (ICIs), rates of immune-related adverse events (irAEs) are similar to those reported in patients without autoimmune diseases, with most symptoms being manageable.

The findings, from a small retrospective study presented at the American College of Rheumatology (ACR) 2019 Annual Meeting, also provide evidence for the efficacy of ICIs in cancer patients with autoimmune diseases, who have largely been excluded from ICI clinical trials. [Efuni E, at al, ACR 2019, abstract 1339]

The study included 84 patients with pre-existing autoimmune diseases who developed malignancy and were treated with anti–CTLA-4 or anti–PD-1 therapy at a single institution between 2011 and 2018. The primary endpoints were the incidence of irAEs and the incidence of autoimmune disease flares.

Among the 22 patients with RA (median age, 67 years; 73 percent female), the majority (n=20; 91 percent) had no evidence of active disease as indicated by their treating physician. Seven patients (32 percent) had melanoma, another seven (32 percent) had non-small-cell lung cancer, while the remaining eight had other malignancies.

Pembrolizumab was used in 13 patients (59 percent), while nine patients (41 percent) were treated with nivolumab and four (18 percent) received ipilimumab. At the start of ICI therapy, 16 patients (73 percent) were receiving RA immunomodulatory therapy, while eight (36 percent) were on systemic corticosteroids and seven (32 percent) were on methotrexate.

irAEs were reported in seven patients (32 percent), with only two patients (9 percent) experiencing grade 3 irAEs. The most common toxicities were dermatitis (n=4; 18 percent) and colitis (n=3; 14 percent).

Temporary discontinuation of ICI therapy due to irAEs was required in five patients (23 percent). Only one patient required permanent ICI discontinuation due to irAEs.

RA flares occurred in 12 patients (55 percent). In most of the cases (n=9; 75 percent), the RA flare was treated with oral corticosteroids. Only one patient had to permanently discontinue ICI therapy due to RA flare.

Median overall survival was 10.5 months among patients with RA, after the start of ICIs.

“In our cohort … fewer [patients] had irAEs after initiation of ICIs compared to a rate of 5–60 percent for any-grade irAEs and 7–30 percent for severe irAEs in patients without autoimmune diseases, depending on [the] agent used. Most symptoms were manageable and [only] a minority of patients required discontinuation of cancer-directed therapy,” noted the investigators. “While this is a small cohort, the results of this analysis suggest that patients with RA experience severe irAEs at a rate similar to the population without autoimmune diseases.”

“Further study is warranted to determine if ICIs may be offered to patients with RA as first-line agents when used for an FDA-approved indication. The choice of ICI and its effect on OS in this population also requires further prospective investigation,” they added.