J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Original Article

Volume 13, Number 4, August 2024, pages 142-149

Long-Term Outcome of Eltrombopag With First-Line Immunosuppressive Therapy for Newly Diagnosed Severe Aplastic Anemia

Figure 1. Cumulative incidence of allogenic stem cell transplantation after IST. allo-SCT: allogenic stem cell transplantation; EPAG: eltrombopag; IST: immunosuppressive therapy.

Figure 2. Overall survival (a) and cumulative incidence of CE (b), PR (c), and CR (d) after IST. CE: clonal evolution; CR: complete response; EPAG: eltrombopag; IST: immunosuppressive therapy; PR: partial response.

Figure 3. Hematologic responses over time by lineage. Data on baseline, 1, 3, and 6 months after the start of IST were collected. (a) Neutrophil. (b) Reticulocyte. (c) Platelet. *P < 0.05. **P < 0.01. EPAG: eltrombopag; IST: immunosuppressive therapy.

**Table 1.** Comparison of Baseline Characteristics of Non-EPAG and EPAG Patients
Baseline characteristics	Non-EPAG (n = 81)	EPAG (n = 20)	P
ATG: antithymocyte globulin; EPAG: eltrombopag; HLA: human leukocyte antigen.
Median age at ATG administration (range)	52 (15 - 65)	53 (18 - 65)	0.78
Camitta criteria, n (%)
Severe	51 (63.0)	10 (50.0)	0.32
Very severe	30 (37.0)	10 (50.0)
Karyotype, n (%)
Normal	71 (87.7)	17 (85.0)	0.58
Others	7 (8.6)	3 (15.0)
Missing	3 (3.7)	0 (0.0)
Sex, n (%)
Female	39 (48.1)	6 (30.0)	0.21
Male	42 (51.9)	14 (70.0)
HLA-matched sibling donor, n (%)
Identified	14 (17.3)	3 (15.0)	1
Median baseline blood cell count (range)
Neutrophil (/µL)	308 (0 - 2,842)	239.0 (45 - 928)	0.82
Platelet (× 10⁴/µL)	0.70 (0.10 - 4.70)	0.85 (0.10 - 1.80)	0.95
Reticulocyte (× 10⁴/µL)	1.42 (0.08 - 6.06)	1.33 (0.37 - 4.10)	0.91
Median follow-up months (range)	64.0 (7.4 - 153.1)	29.0 (4.6 - 60.4)	< 0.001

Table 1. Comparison of Baseline Characteristics of Non-EPAG and EPAG Patients

Baseline characteristics

Non-EPAG (n = 81)

EPAG (n = 20)

ATG: antithymocyte globulin; EPAG: eltrombopag; HLA: human leukocyte antigen.

Median age at ATG administration (range)

52 (15 - 65)

53 (18 - 65)

0.78

Camitta criteria, n (%)

Severe

51 (63.0)

10 (50.0)

0.32

Very severe

30 (37.0)

10 (50.0)

Karyotype, n (%)

Normal

71 (87.7)

17 (85.0)

0.58

Others

7 (8.6)

3 (15.0)

Missing

3 (3.7)

0 (0.0)

Sex, n (%)

Female

39 (48.1)

6 (30.0)

0.21

Male

42 (51.9)

14 (70.0)

HLA-matched sibling donor, n (%)

Identified

14 (17.3)

3 (15.0)

Median baseline blood cell count (range)

Neutrophil (/µL)

308 (0 - 2,842)

239.0 (45 - 928)

0.82

Platelet (× 10⁴/µL)

0.70 (0.10 - 4.70)

0.85 (0.10 - 1.80)

0.95

Reticulocyte (× 10⁴/µL)

1.42 (0.08 - 6.06)

1.33 (0.37 - 4.10)

0.91

Median follow-up months (range)

64.0 (7.4 - 153.1)

29.0 (4.6 - 60.4)

< 0.001

**Table 2.** The Reason for Proceeding to allo-SCT
	Non-EPAG	EPAG	P
allo-SCT: allogenic stem cell transplantation; EPAG: eltrombopag; IST: immunosuppressive therapy.
Insufficient response of IST, n (%)	7 (8.6)	1 (5)	1
Clonal evolution, n (%)	4 (4.9)	0 (0)	0.58
Relapse, n (%)	3 (3.7)	0 (0)	1

Table 2. The Reason for Proceeding to allo-SCT

Non-EPAG

EPAG

allo-SCT: allogenic stem cell transplantation; EPAG: eltrombopag; IST: immunosuppressive therapy.

Insufficient response of IST, n (%)

7 (8.6)

1 (5)

Clonal evolution, n (%)

4 (4.9)

0 (0)

0.58

Relapse, n (%)

3 (3.7)

0 (0)

**Table 3.** Multivariate Analysis on Cumulative Incidence of allo-SCT
Variable	HR (95% CI)	P
allo-SCT: allogenic stem cell transplantation; CI: confidence interval; EPAG: eltrombopag; HR: hazard ratio.
Group
Non-EPAG	1	0.36
EPAG	0.34 (0.032 - 3.52)
Age
16 - 49	1	0.042
50+	0.32 (0.11 - 0.95)
Severity
Severe	1	0.71
Very severe	1.22 (0.43 - 3.47)
Sibling donor
Not identified	1	< 0.01
Identified	6.14 (2.03 - 18.58)

Table 3. Multivariate Analysis on Cumulative Incidence of allo-SCT

Variable

HR (95% CI)

allo-SCT: allogenic stem cell transplantation; CI: confidence interval; EPAG: eltrombopag; HR: hazard ratio.

Group

Non-EPAG

0.36

EPAG

0.34 (0.032 - 3.52)

Age

16 - 49

0.042

50+

0.32 (0.11 - 0.95)

Severity

Severe

0.71

Very severe

1.22 (0.43 - 3.47)

Sibling donor

Not identified

< 0.01

Identified

6.14 (2.03 - 18.58)

**Table 4.** Summary of the Patient Characteristics Who Developed CE After IST
Age	Sex	Group	Diagnosis	Karyotype before IST	Karyotype at CE	Months from IST to CE
AML: acute myeloid leukemia; CE: clonal evolution; CHIP: clonal hematopoiesis of indeterminate potential; EPAG: eltrombopag; F: female; IST: immunosuppressive therapy; M: male; MDS: myelodysplastic syndrome.
37	F	Non-EPAG	MDS	46, XX [20]	46, XX [20]	3.7
54	M	Non-EPAG	AML	Missing	46, XX, add(7)(q22) [20]	5.0
38	M	Non-EPAG	MDS	46, Y, ?t(X; 6)(q26; q21) [1]/46, XY [12]	46, Y, t(X; 11)(q28; p11. 2) [7]/46, XY [13]	11.7
58	F	EPAG	CHIP	46, XX [20]	46, XX, del(6)(q?) [4]/46, XX [16]	17.9
54	F	Non-EPAG	CHIP	46, XX [20]	47, XX, +21	25.3
62	M	Non-EPAG	MDS	45,X,-Y [3]/46, XY [17]	45, X,-Y [16]/45,idem,?t(7;8)(q32;q22) [1]/46, XY [3]	42.3
46	M	Non-EPAG	MDS	46, XY [20]	46, XY, +1, der(1; 7)(q10; p10) [4]/46, XY [16]	67.7
62	F	Non-EPAG	MDS	46, XX [20]	44, XX, add(2)(p11.2), -9, add(15)(q15), -18, add(21)(q22.1) [12]/45, idem, -add(21), +add(21)(q22.1)x2 [3]/46, XX [1]	114.1

Table 4. Summary of the Patient Characteristics Who Developed CE After IST

Age

Sex

Group

Diagnosis

Karyotype before IST

Karyotype at CE

Months from IST to CE

AML: acute myeloid leukemia; CE: clonal evolution; CHIP: clonal hematopoiesis of indeterminate potential; EPAG: eltrombopag; F: female; IST: immunosuppressive therapy; M: male; MDS: myelodysplastic syndrome.

Non-EPAG

MDS

46, XX [20]

3.7

Non-EPAG

AML

Missing

46, XX, add(7)(q22) [20]

5.0

Non-EPAG

MDS

46, Y, ?t(X; 6)(q26; q21) [1]/46, XY [12]

46, Y, t(X; 11)(q28; p11. 2) [7]/46, XY [13]

11.7

EPAG

CHIP

46, XX [20]

46, XX, del(6)(q?) [4]/46, XX [16]

17.9

Non-EPAG

CHIP

46, XX [20]

47, XX, +21

25.3

Non-EPAG

MDS

45,X,-Y [3]/46, XY [17]

45, X,-Y [16]/45,idem,?t(7;8)(q32;q22) [1]/46, XY [3]

42.3

Non-EPAG

MDS

46, XY [20]

46, XY, +1, der(1; 7)(q10; p10) [4]/46, XY [16]

67.7

Non-EPAG

MDS

46, XX [20]

44, XX, add(2)(p11.2), -9, add(15)(q15), -18, add(21)(q22.1) [12]/45, idem, -add(21), +add(21)(q22.1)x2 [3]/46, XX [1]

114.1

**Table 5.** Grade 3-4 Non-Hematological Adverse Events Within 1 Year After IST
	Non-EPAG (n = 81), n (%)	EPAG (n = 20), n (%)	P
EBV: Epstein-Barr virus; EPAG: eltrombopag; IST: immunosuppressive therapy.
EBV reactivation	2 (2.5)	0 (0.0)	1
Kidney dysfunction	7 (8.6)	0 (0.0)	0.34
Liver dysfunction	11 (13.6)	1 (5.0)	0.45
Infection	33 (40.7)	4 (20.0)	0.12
Febrile neutropenia	27 (33.3)	2 (10.0)	0.052

Table 5. Grade 3-4 Non-Hematological Adverse Events Within 1 Year After IST

Non-EPAG (n = 81), n (%)

EPAG (n = 20), n (%)

EBV: Epstein-Barr virus; EPAG: eltrombopag; IST: immunosuppressive therapy.

EBV reactivation

2 (2.5)

0 (0.0)

Kidney dysfunction

7 (8.6)

0 (0.0)

0.34

Liver dysfunction

11 (13.6)

1 (5.0)

0.45

Infection

33 (40.7)

4 (20.0)

0.12

Febrile neutropenia

27 (33.3)

2 (10.0)

0.052