Real-world experience of treatment with thrombopoietin receptor agonists in anti-thymocyte globulin-naïve patients with aplastic anemia: an observational retrospective analysis in a single institution

Figures & data

Table 1. Baseline patient characteristics

Patients	n = 45
Age (years), median (range)	76.5 (44–88)
Sex (female/male), n (%)	27/18 (60/40)
Severity at eltrombopag initiation, n (%)
Severe aplastic anemia	10 (22)
Non-severe aplastic anemia	35 (78)
Count at eltrombopag initiation
Reticulocyte [×10^6/L], median (range)	41,580 (7840–80,860)
Hemoglobin [g/dL], median (range)	8.6 (5.0–14.8)
Neutrophil [×10^6/L], median (range)	925 (120–6622)
Platelet [×10^9/L], median (range)	16 (2–109)
Time from diagnosis to eltrombopag (months), median (range)	5.7 (2.2–18.3)
Karyotype, n (%)
Normal	38 (84)
Abnormal	4 (9)
Unknown	3 (7)
PNH clone, n (%)
Positive (≥1%)	8 (18)
Negative (<1%)	34 (75)
Unknown	3 (7)
Transfusion dependency, n (%)
Platelet	5 (11)
Red blood cell	7 (16)
No. prior treatments, median (range)	1 (1–2)
Prior treatment, n (%)
Cyclosporine A	45 (100)
Metenolone acetate	38 (84)
Prednisolone	2 (4)
Platelet response eligible (platelets <10×10^9/L or transfusion-dependent), n (%)	43 (96)
Erythroid response eligible (hemoglobin <9 g/dL or transfusion dependent), n (%)	29 (64)
Neutrophil response eligible (<1×10^9/L), n (%)	29 (64)
Trilineage response eligible, n (%)	16 (36)

PNH, paroxysmal nocturnal hemoglobinuria.

Figure 1. Eltrombopag dose over time. Box plot indicating median (internal horizontal line), 25th and 75th percentiles (lower and upper box limits, respectively) and 5th–95th percentile (bars).

Table 2. Outcome of TPO-RA treatment.

Patients	n = 45
Type of TPO-RA, n (%)
Eltrombopag alone	40 (89)
Eltrombopag followed by romiplostim	5 (11)
Maximal dose of TPO-RA
Eltrombopag [mg], median (range)	100 (50–100)
Romiplostim [μg/kg], median (range)	20 (15–20)
Maintenance dose of TPO-RA
Eltrombopag [mg], median (range)	75 (12.5–100)
Romiplostim [μg/kg], median (range)	20 (15–20)
Concomitant treatment, n (%)
Cyclosporine A	43 (96)
Metenolone acetate	29 (64)
None	6 (13)
Time to response
At least unilineage [days], median (range)	84 (6–1027)
Trilineage [days], median (range)	397 (185–656)

TPO-RA, thrombopoietin receptor agonist.

Figure 2. Response to TPO-RA by lineage. (A) Number of responders in each lineage at 6 months. (B) Best response during the entire follow-up period. Yellow, platelet; red, erythroid; blue, neutrophil responses.

Figure 3. Response to TPO-RA treatment over time by lineage. (A) neutrophil, (B) erythroid, and (C) platelet responses. Box plots indicate median (internal horizontal line), 25th and 75th percentiles (lower and upper box limits, respectively) and 5th–95th percentile (bars).

Table 3. Hematologic response to TPO-RAs by lineage.

		Response
		6 months	Best response
	Eligible, n	n (%)	n (%)
Any response	45	28 (62)	38 (84)
Platelet	43	16 (37)	24 (56)
Erythroid	29	8 (28)	11 (38)
Neutrophil	29	15 (52)	22 (76)
Trilineage	16	2 (13)	4 (25)

TPO-RA, thrombopoietin receptor agonist.

Table 4. Adverse events during TPO-RA treatment.

n = 45	Any grade	Grade 3–4	Grade 5
	Patients, n (%)
Any adverse event	18 (40)	3 (7)	5 (11)
Anorexia	3 (7)	0	0
Nausea	3 (7)	0	0
Lung infection	3 (7)	0	2 (4)
Oral submucosal hemorrhage	2 (4)	0	0
Blood aspartate aminotransferase increased	2 (4)	1 (2)	0
Blood alanine aminotransferase increased	2 (4)	1 (2)	0
Blood bilirubin increased	2 (4)	0	0
Headache	2 (4)	0	0
Febrile neutropenia	2 (4)	2 (4)	0
Urinary tract infection	1 (2)	0	1 (2)
Leukemia	1 (2)	0	1 (2)
Myelodysplastic syndrome	1 (2)	0	1 (2)
Hyperglycemia	1 (2)	0	0
Abdominal pain upper	1 (2)	0	0
Hemorrhoidal hemorrhage	1 (2)	0	0
Skin rash	1 (2)	0	0
Vomiting	1 (2)	0	0
Blood creatinine increased	1 (2)	0	0

TPO-RA, thrombopoietin receptor agonist.

Table 5. Univariate analysis of factors for response to eltrombopag.

Factors		Patients, n	Response at least unilineage at 6 months (%)	p value^a
Age	<75 vs ≥75 years old	19 vs 26	68 vs 58	0.543
Sex	female vs male	27 vs 18	56 vs 72	0.351
AA severitiy	non-severe vs severe	35 vs 10	60 vs 70	0.719
PNH clone	<1 vs ≥1%	34 vs 8	71 vs 50	0.406
Absolute neutrophil count	<1.0 vs ≥1.0×10^9/L	27 vs 18	63 vs 61	1.000
Reticulocyte count	<40 vs ≥40×10^9/L	21 vs 24	52 vs 71	0.233
Platelet count	<20 vs ≥20×10^9/L	28 vs 17	64 vs 59	0.759
Maintenance dose of eltrombopag	<75 vs ≥75 mg/day	18 vs 27	50 vs 69	0.216
Time from AA diagnosis	<6 vs ≥6 months	24 vs 21	75 vs 48	0.0727

AA, aplastic anemia; PNH, paroxysmal nocturnal hemoglobinuria.

^a Fisher's exact test.