The presence of antinuclear antibodies (ANAs) in patients with advanced non-small cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) inhibitors may be associated with poor outcomes, according to study results published in Lung Cancer.
Further, although immune-related adverse events (irAEs) did not differ according to ANA positivity or negativity, increased ANA titers were associated with an increased incidence of irAEs. Patients with higher antibody titers may, therefore, need careful monitoring, concluded these researchers.
“ANA comprise a spectrum of autoantibodies that react with various nuclear and cytoplasmic components of normal human cells. Although ANA are an important serological marker for certain autoimmune diseases, they have also been detected in serum of various cancer patients as frequently as in individuals with rheumatoid arthritis or systemic lupus erythematosus,” wrote Yasuto Yoneshima, MD, assistant professor, Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, and colleagues.
“This finding has suggested that ANA might be associated with carcinogenesis and represent a state of pre-autoimmunity or immunologic abnormality. Whether such an abnormality might affect the safety or efficacy of has remained unknown,” they added.
Dr. Yoneshima and fellow researchers undertook this retrospective study, therefore, in patients with advanced (stage III or IV) or recurrent NSCLC to determine whether the presence of ANAs has any effect on the safety and efficacy of PD-1 inhibitors.
They included 83 patients treated with either single-agent nivolumab or pembrolizumab (median age: 67 years; 80.7% male; 69.9% adenocarcinoma; 61.4% stage IV disease). In all, 21.7% were positive for ANA (cutoff: 1:40 serum dilution). At treatment initiation, none had any active symptoms of autoimmune disease.
The incidence of irAEs was similar in both groups (ANA: 33.3%; ANA-negative: 32.3%), and was increased in proportion to increasing ANA titer levels.
Researchers analyzed ANA levels in 10 of the 18 patients initially ANA-positive during PD-1 inhibitor treatment. ANA titers increased in three, who all developed irAEs, which included interstitial lung disease (2) and hypothyroidism (1).
Among the 65 patients initially negative for ANA, researchers continued to analyze ANA status in 20 during the course of PD-1 inhibitor treatment. Only one became ANA-positive, but did not go on to develop any irAEs.
Objective response rates in patients who were ANA-positive were similar compared with those who were ANA-negative (27.8% vs 29.2%, respectively). Disease control rates in the two groups were significantly lower, however, in the ANA-positive group (55.6% vs 64.6%).
Patients with ANAs had a significantly shorter progression-free survival (PFS) compared with those without (2.9 vs 3.8 months, respectively; P=0.03), as well as shorter overall survival (OS; 11.6 vs 15.8 months; P=0.03).
After adjusting for ANA, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), and clinical stage of cancer, researchers found that the presence of ANAs remained a significant adverse prognostic indicator for PFS (HR: 2.06; 95% CI: 1.10-3.70; P=0.02) and OS (HR: 2.31; 95% CI: 1.09-4.64; P=0.03).
“ANA levels may provide a measure of immune reactivity in assessment of the toxicity and efficacy of ICI treatment,” concluded Dr. Yoneshima and colleagues. “The results of our study suggest that the immune system of patients with high ANA titers might be more reactive and therefore more likely to give rise to irAEs on exposure to ICIs, and that such patients should be monitored closely during PD-1 inhibitor treatment.”