Efficacy and Feasibility of Programmed Death-1/Programmed Death Ligand-1 Blockade Therapy in Non-Small Cell Lung Cancer Patients With High Antinuclear Antibody Titers

Abstract

BackgroundImmune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce.MethodsThis study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed.ResultsOne hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39–84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group (p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups.ConclusionThe administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group.

Evaluation of autoantibodies as predictors of treatment response and immune‐related adverse events during the treatment with immune checkpoint inhibitors: A prospective longitudinal pan‐cancer study

“…To date, the majority of published studies that evaluated different autoantibodies as biomarkers for safety and efficacy of ICI treatment were conducted in advanced or metastatic NSCLC patients. 18,[21][22][23][24][25] Two studies considered additional autoantibodies besides ANA. Toi et al 23 retrospectively analyzed 137 patients with NSCLC and found out that individuals with preexisting antibodies (ANA, rheumatoid factor, antithyroglobulin, antithyroid peroxidase) at treatment initiation had more favorable outcome as indicated by PFS as compared to patients without antibodies.…”

Safety and Efficacy of PD-1/PD-L1 Inhibitors in Cancer Patients With Preexisting Autoantibodies

“…( 8 ) reported metastatic NSCLC patients positive for ANA had significantly prolonged PFS and OS, which contradicts the conclusion reached by another study ( 7 ). The other two studies ( 5 , 6 ) suggested that the efficacy and safety of ICIs therapy in patients with NSCLC and positive ANA were comparable to those negative for ANA. Accordingly, there was no significant difference in the incidence of irAEs, ORR, and survival outcome between the 16 NSCLC patients positive for ANA and 30 NSCLC patients negative for ANA retrieved from our cohort (data not shown).…”

“…As for the effect of ANA titer, the study of Mouri et al. ( 5 ) suggested the incidence of irAEs was not significantly different between the ANA-positive and ANA-negative groups, regardless of the cutoff of ANA titers (1:40 or 1:80). Our results also reached the similar conclusion that patients with preexisting ANA had no increased risk of irAEs, regardless of the cutoff of ANA titers (1:80 or 1:160) (data not shown).…”

“…There were five published studies estimating the effect of ANA on ICIs toxicity and efficacy ( 5 – 9 ). Four of the studies included only patients with NSCLC ( 5 – 8 ). Giannicola et al.…”

“…Given that ANA positivity may indicate a predisposition to immune activation, it is understandable that some clinicians are concerned that patients positive for ANA may be at a higher risk of irAEs ( 4 ). However, the effect of ANA on the safety and efficacy of ICIs in cancer patients is still controversial ( 5 – 9 ). Moreover, antithyroid antibody was suggested to be associated with thyroid dysfunction after ICIs treatment ( 6 ).…”