Efficacy and Safety of Ropeginterferon Alfa-2b in Pregnant Women With Myeloproliferative Neoplasms: Case Series of Three Subtypes and Review

Abstract

Managing myeloproliferative neoplasms (MPNs) during pregnancy is challenging due to increased thrombotic risk and limited cytoreductive options. Ropeginterferon alfa-2b (ropeginterferon), a long-acting mono-pegylated interferon, has limited data in this setting. We report a Korean multicenter case series of four pregnancies across MPN subtypes, including prefibrotic/early primary myelofibrosis, essential thrombocythemia, and polycythemia vera. Ropeginterferon was used during pregnancy or prior to conception (250–500 μg every 2–12 weeks) with aspirin and/or low-molecular-weight heparin. Hematologic responses were sustained throughout pregnancy without treatment-limiting adverse events. All pregnancies resulted in live births without major maternal or neonatal complications. Within the limits of a small retrospective series, ropeginterferon appeared to be a feasible cytoreductive option in these MPN pregnancies, including pre-conception and intra-pregnancy use; these preliminary observations warrant confirmation in larger prospective studies.

Graphical Abstract

Myeloproliferative neoplasms (MPNs)—polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)—pose substantial challenges in women of reproductive age,1,2,3 conferring increased thrombotic and obstetric risk through combined physiologic hypercoagulability and a pathologic thrombophilic state.1,3,4 Compared with the general population, MPN pregnancies show higher miscarriage (20–26% vs. 12%) and lower live-birth rates (45–78% vs. 80–89%, worst in PV and PMF),5,6,7,8 with excess maternal thrombosis, hemorrhage, pre-eclampsia, fetal growth restriction, and preterm birth.1,2,4,8,9,10 Because pregnancy is itself a prothrombotic state—conferring an approximately 4- to 5-fold increase in venous thromboembolism risk that rises further in the puerperium—superimposed on the myeloproliferative state, contemporary guidance effectively regards all MPN pregnancies as high-risk, irrespective of conventional disease-based risk stratification.1,4,11

Management is complicated by the teratogenic potential of hydroxyurea and anagrelide,1,3,11,12,13 leaving interferon-alpha as the only established safe cytoreductive option.14,15,16,17 Ropeginterferon alfa-2b (ropeginterferon), a mono-pegylated interferon with an extended half-life, has shown superior tolerability over earlier formulations in non-pregnant patients,18,19 but pregnancy data remain extremely limited.20,21

To address this evidence gap, we report a Korean multicenter case series of ropeginterferon across MPN-subtype pregnancies to expand this limited evidence base and inform clinical decision-making.

This multicenter retrospective case series, following the CARE guidelines,22 included four pregnant women with MPN (prefibrotic/early PMF, ET, and PV) treated with ropeginterferon at four tertiary centers in Korea (2021–2025; Table 1). All consecutive ropeginterferon-treated MPN pregnancies were included, with none excluded. Follow-up (data cutoff February 2026) is ongoing, with postpartum durations of approximately 14, 18, 10, and 43 months for Cases 1–4, and no maternal or infant abnormalities have been observed yet.

Table 1. Patient characteristics and baseline data.

Variables		Case 1	Case 2	Case 3	Case 4
Age at diagnosis, yr		37	41	32	36
Age at pregnancy, yr		38	44	34, 36	40
MPN subtype		Prefibrotic/early PMF	ET	PV	PV
Driver mutation		JAK2 V617F	JAK2 V617F	JAK2 V617F	JAK2 V617F
	Variant allele frequency, %	36.7	N/A	18.55	63.96
	Zygosity	Heterozygous	N/A	Heterozygous	Homozygous
Additional mutations		TET2	None	None	None
MPN risk stratification		MIPSS70+ v2.0 low and IPSET-T intermediate	IPSET-T intermediate	PV low risk	PV low risk
Pregnancy risk stratification		High (PMF, PLT > 1,000 × 109/L)	High (Prior miscarriages, DCDA twin pregnancy)	High (Prior stillbirth)	High (Pan-myelosis, PLT > 1,500 × 109/L)
Prior thrombosis/hemorrhage		No	No	No	No
Prior obstetric complication		None	Miscarriage 3 times	Stillbirth at GA 28 wk	None
Blood cell counts at diagnosis
	White blood cells, × 109/L	10.67	9.67	8.83	13.87
	Hemoglobin, g/dL	15.0	14.4	16.3	18.2
	Hematocrit, %	44.5	41.40	48.1	55.6
	Platelet, × 109/L	854	995	639	821

Risk stratification refers to conventional MPN disease-based thrombosis risk (IPSET-thrombosis, MIPSS70+ v2.0, and age/thrombosis-history–based PV category) and is distinct from pregnancy-associated risk, which was considered high in all four pregnancies owing to the MPN–pregnancy interaction.

MPN = myeloproliferative neoplasm, PMF = primary myelofibrosis, ET = essential thrombocythemia, PV = polycythemia vera, N/A = not applicable, MIPSS70+ v2.0 = Mutation-Enhanced International Prognostic Scoring System for Transplantation-Age Patients with Primary Myelofibrosis, IPSET-T = International Prognostic Score for Thrombosis in Essential Thrombocythemia, PLT = platelets, DCDA = dichorionic diamniotic.

The hematologic target in pregnancy is deliberately more permissive than the non-pregnant goal of normalization (e.g., < 400 × 10⁹/L): we adopted a 400–600 × 10⁹/L platelet target to balance thrombosis prevention against over-treatment and maternal cytopenia, while avoiding extreme thrombocytosis (> 1,000–1,500 × 10⁹/L) (Supplementary Table 1).1,4,11,13,23

Clinical data—treatment exposure, concomitant antithrombotic therapy, hematologic parameters, and obstetric and neonatal outcomes—were collected from electronic medical records.

A 37-year-old woman with incidental leukocytosis and thrombocytosis was diagnosed as JAK2 V617F-positive prefibrotic/early PMF according to the 2022 World Health Organization classification criteria,24 with a hypercellular marrow (60–80%) and grade 1 reticulin fibrosis. Risk stratification using Mutation-Enhanced International Prognostic Scoring System for Transplantation-Age Patients with Primary Myelofibrosis (MIPSS70+ v2.0) and revised International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET)-thrombosis indicated low and intermediate risk, respectively, and aspirin 100 mg daily was initiated.

Eleven months later, she presented at 5 weeks of gestation with marked thrombocytosis and leukocytosis (Fig. 1A). Although conventionally low-risk by MIPSS70+ v2.0, her pregnancy was regarded as high-risk owing to intermediate thrombosis risk (revised IPSET-thrombosis), marked thrombocytosis, and the proliferative prefibrotic/early PMF phenotype. Therefore, ropeginterferon was initiated at 250 μg subcutaneously, then escalated to 500 μg every 4 weeks by 13 weeks of gestation, with aspirin and prophylactic low-molecular-weight heparin (LMWH).

Fig. 1. Treatment course and complete blood cell count trends in the four pregnant women with myeloproliferative neoplasms. Platelet count (red circles, left Y-axis) and hematocrit (blue squares, right Y-axis) are plotted against gestational age. The shaded band indicates the platelet target range (400–600 × 10⁹/L), delimited by dashed boundary lines. The dashed vertical line marks delivery. Each purple downward arrow represents an individual ropeginterferon alfa-2b dose given at that gestational age, with the arrow length proportional to the dose; the value below each arrow is the administered dose in micrograms (µg). The header bar above each panel indicates the treatment status during gestation; in (B) it denotes that ropeginterferon was intentionally held throughout pregnancy after confirmation of conception, so that the exposure shown is pre-pregnancy only. (A) Case 1: prefibrotic/early PMF, (B) Case 2: essential thrombocythemia with twin pregnancy, (C) Case 3: polycythemia vera with a history of stillbirth, (D) Case 4: polycythemia vera with rebound pan-myelosis.

PMF = primary myelofibrosis.

Platelet counts fell to 585 × 10⁹/L by 22 weeks, and were maintained within the 400–600 × 10⁹/L target, achieving a complete hematologic response. Transient grade 1 transaminase elevation and fever resolved without dose modification (Supplementary Table 1).

Fetal growth and placental function remained normal throughout pregnancy. Elective cesarean section at 39 weeks resulted in a healthy male infant. At 14 months postpartum, both mother and infant remained well.

This case suggests ropeginterferon may support adequate hematologic control and favorable obstetric outcomes even in prefibrotic/early PMF.

A 41-year-old woman with a history of three miscarriages was diagnosed with JAK2 V617F–positive ET. Although her ET was intermediate-risk by conventional disease-based thrombosis criteria (IPSET-T), her pregnancy was regarded as high-risk owing to a history of recurrent pregnancy loss. One year prior to planned assisted reproduction, treatment with aspirin and ropeginterferon (500 μg every 2 weeks) was initiated.

Hematologic parameters stabilized within 4–6 weeks, and a total of 18 doses were administered over 10 months. Following successful conception of dichorionic diamniotic twins, ropeginterferon was discontinued, and the patient was closely monitored throughout pregnancy.

Hematologic parameters remained stable after discontinuation throughout pregnancy (hemoglobin 12.2–14.1 g/dL; platelet count 296–472 × 10⁹/L; white blood cell count 4.65–14.8 × 10⁹/L) (Fig. 1B). Transient grade 1 headache, myalgia, and transaminase elevation at initiation resolved spontaneously (Supplementary Table 1).

The pregnancy course was uneventful, without thrombosis, hemorrhage, placental complications, or fetal loss. At 37 + 4 weeks of gestation, elective cesarean section resulted in the delivery of two healthy female infants with normal birth weights (2,890 g and 2,820 g, respectively; Supplementary Table 1).

This case suggests preconception control followed by discontinuation during pregnancy can sustain disease stability and favorable outcomes in this high-risk ET pregnancy with recurrent gestational loss.

A 36-year-old woman with JAK2 V617F–positive PV (diagnosed at 32 years of age) had a history of unexplained stillbirth at 28 weeks of gestation during a pregnancy at 34 years of age. Although low-risk by conventional disease-based PV criteria, subsequent pregnancy was regarded as high-risk owing to the prior stillbirth. She was therefore started on low-dose aspirin and ropeginterferon (500 μg every 12 weeks) before attempting a subsequent pregnancy.

A complete hematologic response was achieved after two doses, and she conceived approximately one year later. Hematologic parameters remained stable throughout pregnancy (hemoglobin 11.2–14.5 g/dL; hematocrit 31.8–43.9%; platelet count 229–514 × 10⁹/L; white blood cell count 6.14–12.49 × 10⁹/L) (Fig. 1C) without obstetric complications or recurrent stillbirth; a healthy male infant was delivered by cesarean section at 39 weeks (Supplementary Table 1).

This case suggests ropeginterferon may support disease control and favorable outcomes in PV with prior adverse obstetric history.

A 36-year-old nulligravid woman with JAK2 V617F–positive PV had been treated with hydroxyurea, anagrelide, and aspirin. Following the confirmation of her first pregnancy (5 weeks of gestation) at age 40, cytoreductive agents were discontinued, while aspirin was continued.

Two weeks later, marked rebound pan-myelosis developed, with the platelet count peaking at 2,074 × 10⁹/L (white blood cell count 35.55 × 10⁹/L; hematocrit 47.4%). Given the high thrombotic and bleeding risk—and although low-risk by conventional disease-based criteria, her pregnancy was managed as high-risk owing to the severe rebound pan-myelosis—ropeginterferon was reactively initiated at a platelet count of 1,762 × 10⁹/L (at gestational age 13–14 weeks), with rapid dose escalation (maximum 500 μg by the third visit) (Fig. 1D); only transient grade 1 transaminase elevation occurred.

A partial response was achieved within 8–10 weeks (platelet 687 × 10⁹/L), with subsequent disease control; a healthy male infant was delivered by cesarean section at 38 weeks (Supplementary Table 1).

This case illustrates a reactive rapid-escalation strategy when urgent control is required. The patient was previously published by Bang and Lee20; with the journal’s permission and the patient’s consent, the case is included here—without new clinical data—to contrast reactive rescue with the planned preconception approach of Cases 2 and 3.

In all four pregnancies, ropeginterferon was associated with durable hematologic responses and favorable outcomes. These outcomes appear promising relative to historical cohorts managed with aspirin and/or LMWH,25 particularly given the high-risk pregnancy features such as prior obstetric complications or marked thrombocytosis; however, this uncontrolled comparison should be interpreted with caution.1,3,4,11,26,27 Treatment was well tolerated, with no congenital abnormalities, intrauterine death, thrombosis, or major bleeding (Supplementary Table 1). These outcomes are notable against a still-limited evidence base (Table 2).

Table 2. Summary of published studies on interferon therapy use in pregnant patients with myeloproliferative neoplasms.

Type of interferon	Study	Year	Country	No.	Disease	Live birth rate	Comments
Interferon alfa	Maze et al.27	2019	Multi-national	90 out of 1,210a	Mostly ET, PV	Improved	Interferon alfa use was associated with higher unadjusted odds of live birth (odds ratio, 9.7; 95% CI, 2.3–41.0) compared with observation
Peginterferon alfa-2a	Beauverd et al.15	2016	United Kingdom	10	ET	90%	Only one patient underwent miscarriage
Ropeginterferon alfa-2b	Bang and Lee20	2023	South Korea	1	PV	100%	100% live birth without severe adverse events
Ropeginterferon alfa-2b	Tashi et al.21	2026	U.S./Taiwan	4	ET, PV	100%	Minimal transplacental passage; negligible breastmilk secretion
Ropeginterferon alfa-2b	Present study	2026	South Korea	4	prePMF, ET, PV	100%	Live births in all four pregnancies across the represented subtypes (prePMF, ET, PV), including pre-conception exposure
Ropeginterferon alfa-2b	Above all	2023–2026	Global	8 b	prePMF, ET, PV	100%

Bold text highlights the key clinical advancements of this study compared to previous reports.

ET = essential thrombocythemia, PV = polycythemia vera, CI = confidence interval, prePMF = prefibrotic/early primary myelofibrosis.

^aSystematic review and meta-analysis of 22 studies (1,210 pregnancies); interferon subgroup included 6 studies with 90 patients.

^bCase 4 of the present series corresponds to the patient reported by Bang and Lee20; the two rows describe the same patient at different reporting stages. Because the present study includes a previously reported case, the number of subjects is eight rather than nine.

Contemporary recommendations endorse a risk-adapted approach: low-dose aspirin for nearly all MPN pregnancies, LMWH in high-risk or postpartum settings, and cytoreduction reserved for high-risk pregnancies (prior thrombosis, severe MPN-related obstetric complications, or extreme thrombocytosis), for which interferon-alpha is the agent of choice.1,4,11 Within this framework, ropeginterferon offers favorable tolerability, although pregnancy data remain limited to isolated reports and pharmacokinetic findings.20,21

Ropeginterferon was also selected due to practical considerations regarding drug availability in Korea: conventional interferons have largely been discontinued, and peginterferon alfa-2a faces severe global supply shortages. Consequently, ropeginterferon-being approved and reliably accessible domestically-served as the only available interferon at the time.20 In this context, our case series provides several insights.

First, in our limited experience, ropeginterferon was associated with appropriate hematologic responses and favorable pregnancy outcomes in each represented subtype, including prefibrotic/early PMF, a more proliferative phenotype.28,29 However, with only one to two pregnancies per subtype, these observations remain preliminary. Second, preconception control followed by discontinuation during pregnancy (Cases 2 and 3) may maintain disease stability without the need for continuous cytoreduction. Third, dosing strategies can be adapted to specific clinical situations, including rapid dose escalation for rebound pan-myelosis, achieving stabilization within 8–10 weeks.

The safety profile appeared consistent with prior interferon use in pregnancy, with no clinically significant maternal or fetal adverse events observed, and recent pharmacokinetic data showing minimal transplacental passage and negligible breast-milk secretion provide further reassurance.21 None of the mothers breastfed, as all peripartum decisions predated the Tashi et al.21 report; these pharmacokinetic data may now inform individualized counseling.

This study is limited by its small sample size and uncontrolled retrospective design. Given the rarity of MPN pregnancies requiring cytoreduction, continued accumulation and reporting of real-world data will be essential to define the role of ropeginterferon.

In conclusion, real-world data on ropeginterferon in MPN pregnancy remain extremely scarce. Our experience suggests it may be a feasible cytoreductive option for selected high-risk MPN pregnancies; these preliminary observations should be interpreted with caution and warrant confirmation in larger prospective cohorts.

Ethics statement

This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (No. 2601-085-1709), which served as the central reviewing IRB for this multicenter study. The study was conducted in accordance with the Declaration of Helsinki, and all patients provided written informed consent.

SUPPLEMENTARY MATERIAL

Supplementary Table 1

Treatment summary and outcomes of four pregnant women with myeloproliferative neoplasms