Symposium | The treatment landscape for patients with myelofibrosis and anemia

During the European School of Haematalogy (ESH) 4th How to Diagnose and Treat CML/MPN conference, the MPN Hub held a symposium on March 9, 2025, titled Anemia in myelofibrosis: Sequencing therapies to optimize patient outcomes. Here, we share a presentation by Francesco Passamonti, Università degli Studi di Milano, Milan, IT, discussing the treatment landscape for patients with myelofibrosis and anemia.

Firstly, Passamonti provided an overview of current treatment strategies for patients with myelofibrosis (MF)-related anemia, including red blood cell transfusion, erythropoiesis-stimulating agents, androgens, splenectomy, immunomodulatory drug agents, and Janus kinase inhibitors (JAKis).¹ He then discussed key efficacy and safety data from phase III trials of ruxolitinib, fedratinib, pacritinib, and momelotinib, with a focus on anemia.

Ruxolitinib

• The phase III COMFORT-I (NCT00952289) and COMFORT-II (NCT00952289) trials demonstrated the spleen response benefit of ruxolitinib vs placebo and best available therapy (BAT), respectively (Figure 1).^2,3

• The majority of patients treated with ruxolitinib in the COMFORT-I (96%) and COMFORT-II (97%) trials were anemic, and almost 50% of patients in both trials became transfusion dependent.^2–4

• The efficacy of ruxolitinib is dose-dependent, as shown in the phase IIIb JUMP (NCT01493414) trial, which included patients with low platelet (PLT) counts (50 to <100 × 10⁹/L); lower ≥50%  spleen volume reduction (SVR) rates were observed in patients with low PLT counts who received lower doses of ruxolitnib.⁵

• Results from the JUMP trial and a real-world study of adult patients with MF who were treated with ruxolitinib in the US Flatiron database demonstrated that new or worsening anemia was associated with worse overall survival in patients who were nonanemic at baseline.^6,7

• The response to ruxolitinib after 6 months (RR6) model includes anemia as a risk factor for worse survival among patients treated with ruxolitinib.⁸

Fedratinib

• Results from the phase III JAKARTA (NCT01437787),^9,10JAKARTA-2 (NCT01523171),^9,11FREEDOM (NCT03755518),¹² and FREEDOM-2 (NCT03952039)¹³ trials showed that fedratinib has similar efficacy to ruxolitinib in terms of spleen response; however, anemia was a common adverse event.

Pacritinib

• Results from the phase III PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials demonstrated the benefit of pacritinib vs BAT in patients with MF, with no exclusions for baseline anemia or thrombocytopenia in PERSIST-1, and patients with PLT count ≤100 × 10⁹/L  in PERSIST-2 (Figure 2).^14,15

  • A subanalysis from PERSIST-2 showed that patients treated with pacritinib had improved transfusion independence (TI) rates vs BAT when assessed using the Gale criteria (37% vs 7%; p = 0.001) and the SIMPLIFY criteria (24% vs 4.5%; p = 0.013).¹⁶ 

• A pooled analysis from the PERSIST-1 and PERSIST-2 trials found that pacritinib improved SVR35 (23% vs 2%; p = 0.0007) and 50% reduction in total symptom score (TSS; 25% vs 8%; p = 0.0441) vs BAT in patients with PLT count <50 × 10⁹/L (n = 189).¹⁷

Momelotinib 

• In the SIMPLIFY-1 (NCT01969838) trial, momelotinib demonstrated similar SVR35 response rates to ruxolitinib (26.5% vs 29.0%; noninferiority p = 0.011), and improved TI rates (66.5% vs 49.3%; p <0.001) in JAKi-naïve patients (Figure 3).¹⁸

  • Mean hemoglobin levels increased in patients who crossed over from ruxolitinib to momelotinib.¹⁹

• Results from SIMPLIFY-2 showed similar rates of SVR35 response between momelotinib and BAT (7% vs 6%; p = 0.90), while momelotinib was associated with improved TSS50 (26% vs 6%; p = 0.0006) and TI rates (43% vs 21%; p = 0.0012) in JAKi-experienced patients.²⁰

  • Patients who crossed over from BAT to momelotinib had increased mean hemoglobin levels.²¹

• In the phase III MOMENTUM trial (NCT04173494) trial, the TSS50, TI, and SVR35 rates at Week 48 among patients treated with momelotinib were 45%, 57%, and 43%, respectively, and among patients who crossed over from the danazol to momelotinib, the response rates were 50%, 60%, and 13%, respectively.²²

Conclusions

Passamonti concludes by highlighting the following:

• Ruxolitinib and fedratinib can effectively improve splenomegaly; however, they may exacerbate anemia in patients with MF.​

• Results from the PERSIST trials suggest that pacritinib is effective in patients with MF and severe thrombocytopenia.​

• Data from the SIMPLIFY and MOMENTUM trials indicate that momelotinib can improve TI in patients with MF and anemia while also reducing splenomegaly.​

• A tailored approach may be necessary when choosing a JAKi for patients with MF, particularly if the patient presents with or develops anemia or severe thrombocytopenia.

This independent educational activity is supported by GSK. All content is developed independently by the faculty; the funder is allowed no influence on the content.