Checkpoint Inhibitors: Effective in NSCLC Patients With Pre-existing Autoimmune Disease?

The presence of pre-existing autoimmune antibodies was associated with improved clinical benefit but worse immune-related adverse events (irAEs) among advanced non–small-cell lung cancer (NSCLC) patients who received an anti–programmed cell death protein 1 (anti–PD-1) therapy. The study results were recently published in JAMA Oncology.

In an interview with Cancer Network, Liza C. Villaruz, MD, a medical oncologist at UPMC Hillman Cancer Center, described these study findings as “very interesting” and a “a bit surprising” given that immunotherapy is traditionally not the “best of options” for cancer patients with pre-existing autoimmune disease.

Cancer patients who have pre-existing autoimmune disease already have an overactive immune system, and treatment with an immune checkpoint inhibitor can further activate the immune system and lead to dangerous irAEs. Given this, Villaruz said, “It’s really quite fascinating that the presence of the pre-existing autoantibodies actually correlated with better outcomes.”

To conduct the study, researchers retrospectively reviewed the medical records of 137 patients with advanced NSCLC who received single-agent nivolumab or pembrolizumab between 2016 and 2018 at a hospital in Japan. A total of 99 patients received nivolumab and 38 received pembrolizumab.

Blood samples obtained before treatment were evaluated for the presence of pre-existing rheumatoid factor, antinuclear antibody, antithyroglobulin, and antithyroid peroxidase. If a patient’s blood sample had pre-existing antibodies for any of the markers, they were defined as having pre-existing antibodies. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and development of irAEs were assessed.

Most of the patients were men (105 of 137 patients), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (134 of 137 patients), and had a median age of 68 (range, 36–88) years.

Patients who developed irAEs were found to have better outcomes. They had a higher ORR (52% vs 13%; P < .001), DCR (92% vs 49%, P < .001), 12-month PFS rate (44% vs 18%), and 12-month OS rate (76% vs 47%) than those who did not develop irAEs. Patients with pre-existing antibodies also had a more than three times greater odds of developing irAEs, according to a multivariate analysis (odds ratio, 3.25; 95% CI, 1.59–6.65; P = .001).

Similarly, patients with pre-existing antibodies before treatment were found to have better outcomes. They had a higher ORR (41% vs 18%; P = .006), DCR (81% vs 54%; P = .001), and median PFS (6.5 vs 3.5 months) compared with patients without pre-existing antibodies. OS, however, was not statistically different for patients with or without pre-existing antibodies (HR, 0.72; 95% CI, 0.43–1.18; P = .19). The development of irAEs was also more common among patients with pre-existing antibodies than those without (60% vs 32%).

Whether these findings have clinical implications, however, is unclear.

“Even though we see a higher rate of immune-related adverse events in patients with pre-existing auto[immune] antibodies, it’s still a bit unclear to me what to do with these patients,” Villaruz said. “It’s sort of a Catch 22.”

Additionally, treatment standards for lung cancer patients are increasingly including a combination of chemotherapy and immunotherapy rather than single-agent checkpoint inhibitors, limiting the applicability of the study findings. “It’s still to be determined how [these findings] would correlate specifically within that treatment setting,” Villaruz said.