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 1-2, April 2024, pages 12-22

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment

Figure 1. Complete hematological response (CHR) rates and time to CHR. (a) CHR rates at different assessment visits. (b) Graph depicting time to CHR.

Figure 3. Graph demonstrating the mean spleen index change. The diamond indicates the mean value.

Figure 4. The effect of ropeginterferon alfa-2b on JAK2^V617F allelic burden. (a) Graph demonstrating the change of median JAK2^V617F allelic burden (%) during the 52 weeks of treatment. (b) Waterfall plot indicating the change of the JAK2^V617F allelic burden in individual patients after 52 weeks of treatment. Blue color represents the patients who had complete hematological response (CHR).

**Table 1.** Patient Demographics and Baseline Characteristics
^aSpleen size = length × thickness, which was measured by ultrasound. Splenomegaly was recorded in ultrasound reports, being judged mainly based on spleen length. ^bPatients with hematocrit > 45% were generally treated with phlebotomy or erythrocyte apheresis. ECOG: Eastern Cooperative Oncology Group; HU: hydroxyurea; IFN: interferon; PV: polycythemia vera; SD: standard deviation.
Age (years), mean (SD)	53.0 (10.9)
Sex
Male	31 (63.3%)
Female	18 (36.7%)
ECOG performance status score
0	42 (85.7%)
1	7 (14.3%)
PV diagnosis (months), mean (SD)	44.43 (59.0)
History of HU treatment
Intolerance	49 (100%)
Resistance	0
Total duration of HU treatment (days), median (min. - max.)	125.0 (1 - 7,344)
History of prior IFN treatment, N (%)	30 (61.2%)
Total time of prior IFN treatment (days), median (min. - max.)	153.5 (1 - 6,552)
History of phlebotomy or erythrocyte apheresis, N (%)	23 (46.9%)
History of hemorrhage or thrombosis
Previous hemorrhage	6 (12.2%)
Previous thrombosis	9 (18.4%)
Spleen size (cm²)^a, mean (SD)	55.6 (18.8)
Patients with splenomegaly determined by ultrasound^a, N (%)	36 (73.5%)
JAK2^V617F mutation	49 (100%)
Baseline parameters, mean (SD)
Hematocrit (%)	46.0 (5.3)^b
Leukocytes (10⁹/L)	11.4 (9.4)
Platelets (10⁹/L)	478.5 (238.8)
JAK2^V617F allelic burden (%)	58.5 (25.3)

Table 1. Patient Demographics and Baseline Characteristics

^aSpleen size = length × thickness, which was measured by ultrasound. Splenomegaly was recorded in ultrasound reports, being judged mainly based on spleen length. ^bPatients with hematocrit > 45% were generally treated with phlebotomy or erythrocyte apheresis. ECOG: Eastern Cooperative Oncology Group; HU: hydroxyurea; IFN: interferon; PV: polycythemia vera; SD: standard deviation.

Age (years), mean (SD)

53.0 (10.9)

Sex

Male

31 (63.3%)

Female

18 (36.7%)

ECOG performance status score

42 (85.7%)

7 (14.3%)

PV diagnosis (months), mean (SD)

44.43 (59.0)

History of HU treatment

Intolerance

49 (100%)

Resistance

Total duration of HU treatment (days), median (min. - max.)

125.0 (1 - 7,344)

History of prior IFN treatment, N (%)

30 (61.2%)

Total time of prior IFN treatment (days), median (min. - max.)

153.5 (1 - 6,552)

History of phlebotomy or erythrocyte apheresis, N (%)

23 (46.9%)

History of hemorrhage or thrombosis

Previous hemorrhage

6 (12.2%)

Previous thrombosis

9 (18.4%)

Spleen size (cm²)^a, mean (SD)

55.6 (18.8)

Patients with splenomegaly determined by ultrasound^a, N (%)

36 (73.5%)

JAK2^V617F mutation

49 (100%)

Baseline parameters, mean (SD)

Hematocrit (%)

46.0 (5.3)^b

Leukocytes (10⁹/L)

11.4 (9.4)

Platelets (10⁹/L)

478.5 (238.8)

JAK2^V617F allelic burden (%)

58.5 (25.3)

**Table 2.** Treatment-Emergent Adverse Events Occurring in ≥ 10% Patients
System organ class preferred term	Patients (N = 49)
^aFifteen grade 3 AEs were observed in 11 patients. Among them, possible treatment-related TEAEs were observed in eight patients. ^bFour patients (8.2%) had a prior history of grade 1 alanine aminotransferase increase. ^cOne patient (2.0%) had a prior history of grade 1 aspartate aminotransferase increase. ^dThree patients received G-CSF treatment for decrease in the white blood count during the study. ^eThree patients (6.1%) had a prior history of grade 1 gamma-glutamyl transferase increase. ^fTwo patients (4.1%) had a prior history of grade 1 bilirubin increase. COVID-19: coronavirus disease 2019.
Metabolism and nutrition disorder
Hyperuricemia	22 (44.9%)	0	0	0	0	22 (44.9%)
Hypertriglyceridemia	15 (30.6%)	0	3 (6.1%)	0	0	18 (36.7%)
Decreased appetite	5 (10.2%)	0	0	0	0	5 (10.2%)
Infections and infestations
Urinary tract infection	6 (12.2%)	6 (12.2%)	0	0	0	12 (24.5%)
COVID-19	5 (10.2%)	1 (2.0%)	0	0	0	6 (12.2%)
Upper respiratory tract infection	3 (6.1%)	3 (6.1%)	0	0	0	6 (12.2%)
General disorders and administration site conditions
Asthenia	7 (14.3%)	4 (8.2%)	0	0	0	11 (22.4%)
Pyrexia	5 (10.2%)	1 (2.0%)	0	0	0	6 (12.2%)
Skin and subcutaneous tissue disorders
Alopecia	9 (18.4%)	0	0	0	0	9 (18.4%)
Renal and urinary disorders
Proteinuria	8 (16.3%)	2 (4.1%)	0	0	0	10 (20.4%)
Musculoskeletal and connective tissue disorders
Back pain	4 (8.2%)	1 (2.0%)	0	0	0	5 (10.2%)
Hepatobiliary disorders
Hepatic steatosis	8 (16.3%)	0	0	0	0	8 (16.3%)
Nervous system disorders
Hypoesthesia	6 (12.2%)	0	0	0	0	6 (12.2%)
Investigations
Elevated alanine aminotransferase^b	21 (42.9%)	6 (12.2%)	1 (2.0%)	0	0	28 (57.1%)
Elevated aspartate aminotransferase^c	21 (42.9%)	7 (14.3%)	0	0	0	28 (57.1%)
Lowered white blood cell count^d	8 (16.3%)	13 (26.5%)	2 (4.1%)	0	0	23 (46.9%)
Increased gamma-glutamyl transferase^e	12 (24.5%)	6 (12.2%)	2 (4.1%)	0	0	20 (40.8%)
Decreased neutrophil count	8 (16.3%)	8 (16.3%)	2 (4.1%)	0	0	18 (36.7%)
Decreased lymphocyte count	2 (4.1%)	7 (14.3%)	3 (6.1%)	0	0	12 (24.5%)
Increased beta 2 microglobulin urine	12 (24.5%)	0	0	0	0	12 (24.5%)
Decreased platelet count	9 (18.4%)	1 (2.0%)	0	0	0	10 (20.4%)
Decreased weight	9 (18.4%)	3 (6.1%)	0	0	0	12 (24.5%)
Increased blood bilirubin^f	5 (10.2%)	1 (2.0%)	0	0	0	6 (12.2%)
Increased blood alkaline phosphatase	4 (8.2%)	2 (4.1%)	0	0	0	6 (12.2%)
White blood cells urine positive	6 (12.2%)	1 (2.0%)	0	0	0	7 (14.3%)
Increased blood lactate dehydrogenase	7 (14.3%)	0	0	0	0	7 (14.3%)
Antinuclear antibody positive	8 (16.3%)	0	0	0	0	8 (16.3%)
Anemia	8 (16.3%)	3 (6.1%)	0	0	0	11 (22.4%)

Table 2. Treatment-Emergent Adverse Events Occurring in ≥ 10% Patients

System organ class preferred term

Patients (N = 49)

Grade 1

Grade 2

Grade 3^a

Grade 4

Grade 5

Total

n (%)

^aFifteen grade 3 AEs were observed in 11 patients. Among them, possible treatment-related TEAEs were observed in eight patients. ^bFour patients (8.2%) had a prior history of grade 1 alanine aminotransferase increase. ^cOne patient (2.0%) had a prior history of grade 1 aspartate aminotransferase increase. ^dThree patients received G-CSF treatment for decrease in the white blood count during the study. ^eThree patients (6.1%) had a prior history of grade 1 gamma-glutamyl transferase increase. ^fTwo patients (4.1%) had a prior history of grade 1 bilirubin increase. COVID-19: coronavirus disease 2019.

Metabolism and nutrition disorder

Hyperuricemia

22 (44.9%)

Hypertriglyceridemia

15 (30.6%)

3 (6.1%)

18 (36.7%)

Decreased appetite

5 (10.2%)

Infections and infestations

Urinary tract infection

6 (12.2%)

12 (24.5%)

COVID-19

5 (10.2%)

1 (2.0%)

6 (12.2%)

Upper respiratory tract infection

3 (6.1%)

6 (12.2%)

General disorders and administration site conditions

Asthenia

7 (14.3%)

4 (8.2%)

11 (22.4%)

Pyrexia

5 (10.2%)

1 (2.0%)

6 (12.2%)

Skin and subcutaneous tissue disorders

Alopecia

9 (18.4%)

Renal and urinary disorders

Proteinuria

8 (16.3%)

2 (4.1%)

10 (20.4%)

Musculoskeletal and connective tissue disorders

Back pain

4 (8.2%)

1 (2.0%)

5 (10.2%)

Hepatobiliary disorders

Hepatic steatosis

8 (16.3%)

Nervous system disorders

Hypoesthesia

6 (12.2%)

Investigations

Elevated alanine aminotransferase^b

21 (42.9%)

6 (12.2%)

1 (2.0%)

28 (57.1%)

Elevated aspartate aminotransferase^c

21 (42.9%)

7 (14.3%)

28 (57.1%)

Lowered white blood cell count^d

8 (16.3%)

13 (26.5%)

2 (4.1%)

23 (46.9%)

Increased gamma-glutamyl transferase^e

12 (24.5%)

6 (12.2%)

2 (4.1%)

20 (40.8%)

Decreased neutrophil count

8 (16.3%)

2 (4.1%)

18 (36.7%)

Decreased lymphocyte count

2 (4.1%)

7 (14.3%)

3 (6.1%)

12 (24.5%)

Increased beta 2 microglobulin urine

12 (24.5%)

Decreased platelet count

9 (18.4%)

1 (2.0%)

10 (20.4%)

Decreased weight

9 (18.4%)

3 (6.1%)

12 (24.5%)

Increased blood bilirubin^f

5 (10.2%)

1 (2.0%)

6 (12.2%)

Increased blood alkaline phosphatase

4 (8.2%)

2 (4.1%)

6 (12.2%)

White blood cells urine positive

6 (12.2%)

1 (2.0%)

7 (14.3%)

Increased blood lactate dehydrogenase

7 (14.3%)

Antinuclear antibody positive

8 (16.3%)

Anemia

8 (16.3%)

3 (6.1%)

11 (22.4%)

**Table 3.** Summary of PK Parameters
PK parameters	Starting dose (250 µg)	After intra-patient dose titrations (500 µg)
T_max: median time to the maximum serum ropeginterferon alfa-2b concentration; T_1/2: terminal-phase half-life; C_max: maximum serum concentration; C_{max ss}: steady state of maximum serum concentration; AUC_0-t: area under the serum concentration-time curve from time 0 to the time of the last quantifiable sample within a dosing interval; AUC_0-tau: area under the serum concentration-time curve during the dosing interval after repeated dosing; PK: pharmacokinetic; SD: standard deviation.
C_max or C_{max ss} (pg/mL), mean ± SD	18,632.0 ± 10,288.2	59,534.1 ± 22,498.3
T_max (h), median (min. - max.)	96 (48.0 - 168.0)	96 (48.0 - 210.6)
AUC_0-t or AUC_0-tau (h × pg/mL), mean ± SD	3,960,705.9 ± 2,416,333.4	15,293,612.2 ± 5,625,792.8
T_1/2 (h), mean ± SD	144.7 ± 100.0	-

Table 3. Summary of PK Parameters

PK parameters

Starting dose (250 µg)

After intra-patient dose titrations (500 µg)

T_max: median time to the maximum serum ropeginterferon alfa-2b concentration; T_1/2: terminal-phase half-life; C_max: maximum serum concentration; C_{max ss}: steady state of maximum serum concentration; AUC_0-t: area under the serum concentration-time curve from time 0 to the time of the last quantifiable sample within a dosing interval; AUC_0-tau: area under the serum concentration-time curve during the dosing interval after repeated dosing; PK: pharmacokinetic; SD: standard deviation.

C_max or C_{max ss} (pg/mL), mean ± SD

18,632.0 ± 10,288.2

59,534.1 ± 22,498.3

T_max (h), median (min. - max.)

96 (48.0 - 168.0)

96 (48.0 - 210.6)

AUC_0-t or AUC_0-tau (h × pg/mL), mean ± SD

3,960,705.9 ± 2,416,333.4

15,293,612.2 ± 5,625,792.8

T_1/2 (h), mean ± SD

144.7 ± 100.0