Early Changes of Serum Interleukin 14α Levels Predicts the Response to Anti-PD-1 Therapy in Cancer

Abstract

Background: Programmed cell death-1 (PD-1) blockade has been shown to confer clinical benefit in cancer patients. Here, we assessed the level of serum interleukin 14α (IL14α) in patients receiving anti-PD-1 treatment.

Methods: This prospective study recruited 30 patients with advanced solid cancer who received pembrolizumab treatment in Northern Jiangsu People's Hospital between April 2016 and June 2018. The western blot analysis was used to assess the expression level of serum IL14α in patients at baseline and after 2 cycles of treatment. Interleukin 14α was performed using the unpaired 2-tailed Student test. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test.

Results: The early change of IL14α after 2 cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles - IL14α level before treatment)/IL14α level before treatment × 100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (sensitivity = 85.71%, specificity = 62.5%; area under the ROC curve [AUC] = 0.7277, P = .034). Using this cutoff to subgroup the patients, an improved objective response rate was observed in patients with a delta IL14α change higher than 2.46% (P = .0072). A delta IL14α change over 2.46% was associated with a superior PFS (P = .0039).

Conclusions: Early changes of serum IL14α levels may be a promising biomarker to predict outcomes in patients with solid cancer following anti-PD-1 treatment.

Keywords: Interleukin 14α; cancer; prognosis; programmed cell death-1 inhibitor.

Figure 1.

PFS and OS stratified by mean levels of IL14α at (A and B) baseline and (C and D) after 2 cycles of anti-PD-1 therapy. IL14α indicates interleukin 14α; OS, overall survival; PD-1, programmed cell death-1; PFS, progression-free survival.

Figure 2.

Receiver operating characteristic (ROC) analysis predicting therapeutic response after treatments. The crease line indicates AUC of the reference variable (delta IL14α change post 2 cycles); the dotted line indicates the area under the ROC curve (AUC) where the null hypothesis (P < .05) is not rejected, and the variable would have no predictive value. AUC indicates area under the ROC curve; IL14α, interleukin 14α.

Figure 3.

Overall response distribution of patients with cutoff as 2.46% of delta IL14α change. IL14α indicates interleukin 14α; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 4.

(A) PFS and (B) OS stratified by delta IL14α change cutoff (2.46%) after 2 cycles anti-PD-1 therapy. IL14α indicates interleukin 14α; OS, overall survival; PFS, progression-free survival.