Necessity of neutrophil-to-lymphocyte ratio monitoring for hypothyroidism using nivolumab in patients with cancer

Figure 1 Neutrophil-to-lymphocyte ratio fluctuation in patients who discontinued treatment after administering nivolumab < 6 times, who discontinued treatment after administering nivolumab 6-11 times, and who administered nivolumab ≥ 12 times. A: A significant increase in neutrophil-to-lymphocyte ratio (NLR) was observed at the discontinuation (n = 40, median NLR = 4.01 vs 5.92, P = 0.020); B: A significant increase in NLR was observed at the discontinuation (n = 32, median NLR = 3.03 vs 3.50, P = 0.038); C: No significant difference in NLR was observed between treatment initiation and the 12^th administration (n = 32, median NLR = 2.64 vs 2.32, P = 0.940). NLR: Neutrophil-to-lymphocyte ratio.

Figure 2 Relationship between neutrophil-to-lymphocyte ratio and nivolumab treatment continuity. The median numbers of nivolumab administration in each group with mean neutrophil-to-lymphocyte ratio (NLR) < 3.5, 3.5 to < 5, and ≥ 5 were 11.5 (n = 52), 8 (n = 25), and 4 (n = 27), respectively. The groups with mean NLR < 3.5 and 3.5 to < 5 had significantly higher treatment continuity than those with mean NLR ≥ 5 (hazard ratio [HR] for low tertile compared with high tertile: 0.23; 95% confidence interval [CI]: 0.13-0.41, P < 0.001; HR for middle tertile compared with high tertile: 0.32; 95%CI: 0.17-0.60; P < 0.001).

Figure 3 Nivolumab treatment continuity in patients who developed hypothyroidism. Treatment continuity in patients who developed hypothyroidism was significantly longer than in those who did not develop hypothyroidism (n = 104, median not reached vs 7 times administration, P = 0.010).

Figure 4 Relationship between neutrophil-to-lymphocyte ratio and the onset period of hypothyroidism. The median onset periods of each group with maximum neutrophil-to-lymphocyte ratio (NLR) values of < 3.5, 3.5 to < 5, and ≥ 5 were at 5^th (n = 7), 6^th (n = 5), and 9^th administration (n = 9), respectively. The groups with a maximum NLR of < 3.5 had a significantly earlier onset of hypothyroidism than the group with NLR ≥ 5, whereas there was no significant difference in the onset periods of the groups with maximum NLR values of 3.5-5 and ≥ 5 (HR for low tertile compared with highest tertile: 5.33; 95%CI: 1.47-19.33, P = 0.011; HR for middle tertile compared with highest tertile: 3.15; 95%CI: 0.83-11.89, P = 0.091).