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Symposium | Navigating therapeutic options for patients with cytopenic MF

By Jen Wyatt Green

Featured:

Steffen Koschmieder

Jun 30, 2026

Learning objective: After reading this article, learners will be able to evaluate current and emerging therapeutic options for cytopenic myelofibrosis, with a focus on selecting and sequencing treatments for patients.

Do you know... Which of the following therapies have demonstrated efficacy in patients with myelofibrosis and severe thrombocytopenia (platelets <50 × 109/L)?

At the ESH 11th Translational Research Conference: Myeloproliferative Neoplasms, April 24–26, 2026, Estoril, PT, the MPN Hub held a symposium, titled Patient-centered approaches in myelofibrosis: Tailoring treatment for anemia and thrombocytopenia. During the symposium, MPN Hub Steering Committee member Steffen Koschmieder, Uniklinikum RWTH Aachen, Aachen, DE, delivered a presentation on navigating therapeutic options for patients with cytopenic myelofibrosis (MF).

Symposium | Navigating therapeutic options for patients with cytopenic MF

In this presentation, Koschmieder discusses current therapeutic approaches to cytopenic MF, including a review of key data on outcomes with momelotinib, pacritinib, luspatercept, and pelabresib and selinexor in combination with ruxolitinib.

Key points

The management of cytopenic MF requires balancing the treatment of cytopenias with MF-directed therapy. Although cytopenias have traditionally been managed with supportive approaches, targeted therapies for cytopenias and cytopenic MF have recently emerged (Figure 1).^1–5
Two targeted therapies are currently approved for the treatment of patients with cytopenic MF.
Momelotinib is approved in the US for adult patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF, with anemia, and in the EU for splenomegaly or other disease-related symptoms in adult patients with moderate to severe anemia who have primary MF, post-PV MF, or post-ET MF and who are Janus kinase inhibitor (JAKi)-naïve or have been treated with ruxolitinib.^6,7
Pacritinib is approved in the US for adult patients with intermediate or high-risk MF, including primary MF, post-PV MF, or post-ET MF, with a platelet count <50 × 10⁹/L.⁸

Figure 1. Supportive care and targeted therapies for cytopenic myelofibrosis*

*Adapted from Reynolds et al, Passamonti et al, Koschmieder et al, Gangat, et al, and Mascarenhas et al.^1–5
EESA, erythropoiesis-stimulating agent; IMiD, immunomodulatory drug; JAKi, Janus kinase inhibitor; TGF-β, transforming growth factor beta.

Momelotinib maintained spleen and symptom control while improving transfusion outcomes across the phase III SIMPLIFY-1 (NCT01969838; N = 432), SIMPLIFY-2 (NCT02101268; N = 156), and MOMENTUM (NCT04173494; N = 195) trials.^9–11
Across these trials, momelotinib maintained or improved hemoglobin levels over time, and 77–87% of patients maintained or improved transfusion intensity vs baseline.^9-12
In a post hoc analysis of the MOMENTUM trial, efficacy was observed across platelet subgroups, including <50 × 10⁹/L (Figure 2), suggesting that the activity of momelotinib may extend beyond anemia to include patients with thrombocytopenia.¹³

Figure 2. MOMENTUM sub-analysis: Outcomes in myelofibrosis with thrombocytopenia*

*Adapted from Kiladjian et al.¹³
BL, baseline; PLT, platelet count; SVR35, spleen volume reduction ≥35%; TI, transfusion independence; TSS50, Total Symptom Score reduction ≥50%.

Pacritinib improved clinical outcomes in patients with MF and thrombocytopenia in the phase III PERSIST-2 trial (NCT02055781), with additional evidence of anemia benefit demonstrated by a sub-analysis of transfusion independence rates.^14–16
Findings from the phase II ACE-536-MF-001 (NCT03194542) and phase II ODYSSEY (NCT06517875) trials demonstrated that luspatercept improved anemia outcomes in patients with MF, with or without JAK inhibitor therapy.^17-19
In the phase III MANIFEST-2 trial (NCT04603495), the addition of pelabresib to ruxolitinib was associated with increased thrombocytopenia and reduced anemia compared with ruxolitinib monotherapy.^21,21
Initial topline results from the phase III SENTRY trial (NCT04562389) demonstrated that selinexor in combination with ruxolitinib improved spleen responses (47% vs 23% at Week 36), with similar symptom improvement vs ruxolitinib monotherapy but with frequent cytopenias (thrombocytopenia, 59% vs 43%; anemia, 57% vs 58%).²²
Emerging therapies may directly improve cytopenias or allow reduced JAK inhibitor dosing without sacrificing efficacy in MF.^2–5

This educational resource is independently supported by GSK. All content is developed by the faculty in collaboration with SES. Funders are allowed no influence.

References

Reynolds SB, Pettit K. New approaches to tackle cytopenic myelofibrosis. Hematology Am Soc Hematol Educ Program. 2022;2022(1):235-244. DOI: 10.1182/hematology.2022000340
Passamonti F, Harrison C, Mesa R, et al. Anemia in myelofibrosis: Current and emerging treatment options. Crit Rev Oncol Hematol. 2022;180:103862. DOI: 10.1016/j.critrevonc.2022.103862
Koschmieder S, Bose P, Ellis MH, et al. Myelofibrosis management in routine clinical practice with a focus on patients with cytopenias: recommendations from a global consensus group. Leukemia. 2024;38(8):1831-1838. DOI: 10.1038/s41375-024-02330-7
Gangat N, Tefferi A, Bose P, et al. RALLY MF: A phase 2 study of DISC-0974, an anti-hemojuvelin antibody, in patients with myelofibrosis and anemia. Blood. 2025; 146 (Supplement 1): 2042. DOI: 10.1182/blood-2025-2042
Mascarenhas J. Safety and efficacy of the mutant calreticulin-specific monoclonal antibody INCA033989 as monotherapy or in combination with ruxolitinib in patients with myelofibrosis: Preliminary results from dose escalation of two global phase 1 studies. Abstract #484. Presented at: 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US.
Momelotinib. Prescribing Information (FDA). 2023. Revised Sep 2023.
Momelotinib. Summary of Product Characteristics (EMA). 2024. Revised May 2025.
Pacritinib. Prescribing Information (FDA). 2022. Revised Feb 2022.
Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor–naïve patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844-3850. DOI: 10.1200/JCO.2017.73.4418
Harrison C, Vannucchi, AM, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): A randomised, open-label, phase 3 trial. Lancet Haematol. 2018;5(2):e73-e81. DOI: 10.1016/S2352-3026(17)30237-5
Verstovsek S, Gerds A, Vannucchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): Results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. DOI: 10.1016/S0140-6736(22)02036-0
Harrison C, Mesa R, Talpaz M, et al. Longitudinal assessment of transfusion intensity in patients with JAK inhibitor-naive or -experienced myelofibrosis treated with momelotinib. Clin Lymphoma Myeloma Leuk. 2025;25(3):199-211. DOI: 10.1016/j.clml.2024.10.001
Kiladjian JJ, et al. Momelotinib in myelofibrosis patients with thrombocytopenia: Post hoc analysis from three randomized phase 3 trials. Hemasphere. 2023;7(11):e963. DOI: 10.1097/HS9.0000000000000963
Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis. JAMA Oncol. 2018;4(5):652-659. DOI: 10.1001/jamaoncol.2017.5818
Verstovek S, Mesa, R, Talpaz, M, et al. Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. Haematologica. 2022;107(7):1599-1607. DOI: 10.3324/haematol.2021.279415
Oh ST, Mesa R, Harrison C, et al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv. 2023;7:5835-5842. DOI: 10.1182/bloodadvances.2023010151
Gerds A, Harrison C, Kiladjian JJ, et al. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. 2024;8(17):4511-4522. DOI: 10.1182/bloodadvances.2024012939
Kiladjian JJ, Harrison C, Mesa R, et al. MPN-346 INDEPENDENCE: Enrolling phase III trial to study the efficacy and safety of luspatercept versus placebo in patients with myelofibrosis on JAK2 inhibitor (JAK2i) therapy requiring red blood cell transfusions (RBCTs). Clin Lymphoma Myeloma Leuk. 2023;23(S390). DOI: 10.1016/S2152-2650(23)01234-X
Bose P. Preliminary experience from the ODYSSEY trial: Efficacy and safety of momelotinib in combination with luspatercept in patients with transfusion-dependent myelofibrosisPoster #3803. Presented at: 67th American Society of Hematology Annual Meeting and Exposition; Dec 6–9, 2025; Orlando, US.
Vannucchi A, et al. Pelabresib in combination with ruxolitinib for Janus kinase inhibitor-naive patients with myelofibrosis: 72-week follow-up with long-term efficacy outcomes of the phase III MANIFEST-2 study. Abstract #S223. Presented at: European Hematology Association 2025 Congress; Jun 12–15 2025; Milan, IT.
Rampal RK, Grosicki S, Chraniuk D, et al. Pelabresib plus ruxolitinib for JAK inhibitor-naive myelofibrosis: A randomized phase 3 trial. Nat Med. 2025;31(5):1531-1538. DOI: 10.1038/s41591-025-03572-3
Targeted Oncology. https://www.targetedonc.com/view/reduced-spleen-volume-observed-in-topline-selinexor-ruxolitinib-trial-results. Published March 24, 2026. Accessed June 10, 2026.
Mascarenhas J, Maher K, Rampal R, et al. Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design. Future Oncol. 025;21(7):807–813. DOI: 10.1080/14796694.2025.2461393

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