J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 13, Number 5, May 2021, pages 268-275

Clinical and Hematological Predictors of High-Grade Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors

**Table 1.** Baseline Characteristics of the Cohort
Patient characteristics (n = 160)	N (%) or median (minimum - maximum)
Categorical variables are summarized using the number (percentage), and numerical variables are summarized using median (minimum - maximum). LN: lymph node; ICI: immune checkpoint inhibitor.
Age at diagnosis (years)	64 (17 - 93)
Gender
Male	79 (49.4%)
Female	81 (50.6%)
Race
African American	38 (23.8%)
Caucasian	122 (76.2%)
Diagnosis
Lung cancer	106 (66.3%)
Melanoma	54 (63.7)
Stage
Stage II or III	57 (35.7%)
Stage IV	103 (64.4%)
Visceral metastatic disease
None	57 (36%)
Single metastatic site	23 (14%)
≥ 2 metastatic sites	80 (50%)
Disease burden
Low	80 (50%)
High	80 (50%)
Status at last check
Alive	130 (81.3%)
Diseased	30 (18.8%)
LN only
No	134 (83.7%)
Yes	26 (16.3%)
Previous systemic treatment
Yes	62 (38.7%)
No	98 (61.3%)
Combination with chemotherapy
Yes	38 (23.7%)
No	122 (76.3%)
ICI and the line of treatment
First-line	48 (30.0%)
Second-line	112 (70.0%)
Treatment agents
Ipilimumab only	5 (3.14%)
Nivolumab only	47 (29.56%)
Ipilimumab + nivolumabo	31 (19.50%)
Pembrolizumab	55 (34.59%)
Durvalumab	14 (8.81%)
Atezolizumab	7 (4.40%)

Table 1. Baseline Characteristics of the Cohort

Patient characteristics (n = 160)

N (%) or median (minimum - maximum)

Categorical variables are summarized using the number (percentage), and numerical variables are summarized using median (minimum - maximum). LN: lymph node; ICI: immune checkpoint inhibitor.

Age at diagnosis (years)

64 (17 - 93)

Gender

Male

79 (49.4%)

Female

81 (50.6%)

Race

African American

38 (23.8%)

Caucasian

122 (76.2%)

Diagnosis

Lung cancer

106 (66.3%)

Melanoma

54 (63.7)

Stage

Stage II or III

57 (35.7%)

Stage IV

103 (64.4%)

Visceral metastatic disease

None

57 (36%)

Single metastatic site

23 (14%)

≥ 2 metastatic sites

80 (50%)

Disease burden

Low

80 (50%)

High

80 (50%)

Status at last check

Alive

130 (81.3%)

Diseased

30 (18.8%)

LN only

134 (83.7%)

Yes

26 (16.3%)

Previous systemic treatment

Yes

62 (38.7%)

98 (61.3%)

Combination with chemotherapy

Yes

38 (23.7%)

122 (76.3%)

ICI and the line of treatment

First-line

48 (30.0%)

Second-line

112 (70.0%)

Treatment agents

Ipilimumab only

5 (3.14%)

Nivolumab only

47 (29.56%)

Ipilimumab + nivolumabo

31 (19.50%)

Pembrolizumab

55 (34.59%)

Durvalumab

14 (8.81%)

Atezolizumab

7 (4.40%)

**Table 2.** Comparison of Characteristics in irAE and Non-irAE Patients
	Non-irAE (n = 114)	irAE (n = 46)	P
SD: standard deviation; LN: lymph node; ICI: immune checkpoint inhibitor; WBC: white blood cell; PLT: platelet; Hb: hemoglobin; ANC: absolute neutrophilic count; ALC: absolute lymphocyte count; irAE: immune-related adverse event.
Sex			0.48
Female	60 (52.63%)	21 (45.65%)
Male	54 (47.37%)	25 (54.35%)
Age (years), mean ± SD	62.5 (± 13.6)	65 (± 9.36)	0.13
Age group			0.38
Younger than 65 years	61 (53.51%)	21 (45.65%)
65 years or older	53 (46.49%)	25 (54.35%)
Race			0.15
African American	31 (27.19%)	7 (15.22%)
Caucasian	83 (72.81%)	39 (84.78%)
Diagnosis			0.06
Lung cancer	81 (71.05%)	25 (54.35%)
Melanoma	33 (28.95%)	21 (45.65%)
Stage			0.06
II or III	46 (40.35%)	11 (23.91%)
IV	68 (59.65%)	35 (76.09%)
Burden of disease			0.05
Low-burden disease	63 (55.26%)	17 (36.96%)
High-burden disease	51 (44.74%)	29 (63.04%)
LN only			0.82
No	95 (83.33%)	39 (84.78%)
Yes	19 (16.67%)	7 (15.22%)
Previous systemic treatment			1.00
No	70 (61.40%)	28 (60.87%)
Yes	44 (38.60%)	18 (39.13%)
ICI and the line of treatment			0.70
First-line	81 (71.05%)	31 (67.39%)
Second-line	33 (28.95%)	15 (32.61%)
Dual agents or immunotherapy?			0.0001
No	101 (88.60%)	28 (60.87%)
Yes	13 (11.40%)	18 (39.13%)
WBC level (k/µL)			0.15
Less than or equal to 10 (n = 121)	90 (78.95%)	31 (67.39%)
Higher than 10 (n = 39)	24 (21.05%)	15 (32.61%)
ALC level (k/µL)			0.56
Less than or equal to 600 (n = 16)	13 (11.40%)	3 (6.52%)
Higher than 600 (n = 144)	101 (88.60%)	43 (93.48%)
			0.34
Less than or equal to 1,000 (n = 48)	37 (32.46%)	11 (23.91%)
Higher than 1,000 (n = 112)	77 (67.54%)	35 (76.09%)
			0.08
Less than or equal to 2,000 (n = 126)	94 (82.46%)	32 (69.57%)
Higher than 2,000 (n = 34)	20 (17.54%)	14 (30.43%)
PLT/ALC ratio (k/µL)			0.21
Less than or equal to 150 (n = 63)	41 (35.96%)	22 (47.83%)
Higher than 150 (n = 97)	73 (64.04%)	24 (52.17%)
WBC (k/µL), mean ± SD	8.29 ± 4.42	8.34 ± 2.67	0.94
Hb (g/dL), mean ± SD	11.89 ± 2.14	12.42 ± 2.00	0.14
PLT (k/µL), mean ± SD	271.08 ± 102.41	259.80 ± 86.80	0.48
ANC (k/µL), mean ± SD	5.61 ± 3.35	5.49 ± 2.25	0.79
ALC (k/µL), mean ± SD	1.39 ± 0.73	1.78 ± 1.36	0.07
ANC/ALC, mean ± SD	5.34 ± 5.19	4.53 ± 3.76	0.27
PLT/ALC, mean ± SD	257.02 ± 205.95	200.62 ± 139.11	0.04
Number of cycles, mean ± SD	13.41 ± 16.71	6.91 ± 7.67	0.001

Table 2. Comparison of Characteristics in irAE and Non-irAE Patients

Non-irAE (n = 114)

irAE (n = 46)

SD: standard deviation; LN: lymph node; ICI: immune checkpoint inhibitor; WBC: white blood cell; PLT: platelet; Hb: hemoglobin; ANC: absolute neutrophilic count; ALC: absolute lymphocyte count; irAE: immune-related adverse event.

Sex

0.48

Female

60 (52.63%)

21 (45.65%)

Male

54 (47.37%)

25 (54.35%)

Age (years), mean ± SD

62.5 (± 13.6)

65 (± 9.36)

0.13

Age group

0.38

Younger than 65 years

61 (53.51%)

21 (45.65%)

65 years or older

53 (46.49%)

25 (54.35%)

Race

0.15

African American

31 (27.19%)

7 (15.22%)

Caucasian

83 (72.81%)

39 (84.78%)

Diagnosis

0.06

Lung cancer

81 (71.05%)

25 (54.35%)

Melanoma

33 (28.95%)

21 (45.65%)

Stage

0.06

II or III

46 (40.35%)

11 (23.91%)

68 (59.65%)

35 (76.09%)

Burden of disease

0.05

Low-burden disease

63 (55.26%)

17 (36.96%)

High-burden disease

51 (44.74%)

29 (63.04%)

LN only

0.82

95 (83.33%)

39 (84.78%)

Yes

19 (16.67%)

7 (15.22%)

Previous systemic treatment

1.00

70 (61.40%)

28 (60.87%)

Yes

44 (38.60%)

18 (39.13%)

ICI and the line of treatment

0.70

First-line

81 (71.05%)

31 (67.39%)

Second-line

33 (28.95%)

15 (32.61%)

Dual agents or immunotherapy?

0.0001

101 (88.60%)

28 (60.87%)

Yes

13 (11.40%)

18 (39.13%)

WBC level (k/µL)

0.15

Less than or equal to 10 (n = 121)

90 (78.95%)

31 (67.39%)

Higher than 10 (n = 39)

24 (21.05%)

15 (32.61%)

ALC level (k/µL)

0.56

Less than or equal to 600 (n = 16)

13 (11.40%)

3 (6.52%)

Higher than 600 (n = 144)

101 (88.60%)

43 (93.48%)

0.34

Less than or equal to 1,000 (n = 48)

37 (32.46%)

11 (23.91%)

Higher than 1,000 (n = 112)

77 (67.54%)

35 (76.09%)

0.08

Less than or equal to 2,000 (n = 126)

94 (82.46%)

32 (69.57%)

Higher than 2,000 (n = 34)

20 (17.54%)

14 (30.43%)

PLT/ALC ratio (k/µL)

0.21

Less than or equal to 150 (n = 63)

41 (35.96%)

22 (47.83%)

Higher than 150 (n = 97)

73 (64.04%)

24 (52.17%)

WBC (k/µL), mean ± SD

8.29 ± 4.42

8.34 ± 2.67

0.94

Hb (g/dL), mean ± SD

11.89 ± 2.14

12.42 ± 2.00

0.14

PLT (k/µL), mean ± SD

271.08 ± 102.41

259.80 ± 86.80

0.48

ANC (k/µL), mean ± SD

5.61 ± 3.35

5.49 ± 2.25

0.79

ALC (k/µL), mean ± SD

1.39 ± 0.73

1.78 ± 1.36

0.07

ANC/ALC, mean ± SD

5.34 ± 5.19

4.53 ± 3.76

0.27

PLT/ALC, mean ± SD

257.02 ± 205.95

200.62 ± 139.11

0.04

Number of cycles, mean ± SD

13.41 ± 16.71

6.91 ± 7.67

0.001