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Zinpentraxin alfa treatment for patients with MF intolerant of or ineligible for ruxolitinib

By Jennifer Reilly

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Mar 6, 2024

Learning objective: After reading this article, learners will be able to cite a new clinical development in myelofibrosis.


Patients with myelofibrosis (MF) are more likely to experience fibrotic changes which can impact the bone marrow (BM) niche, and result in impaired hematopoiesis, anemia, and thrombocytopenia. Zinpentraxin alfa is a recombinant form of the human pentraxin-2 which possesses antifibrotic activity and is being investigated in the treatment of MF.

Here, we summarize a study published by Verstovsek et al.1 in Haematologica on results from the randomized phase II trial (NCT01981850) of zinpentraxin alfa in patients with MF who are ineligible for, intolerant of, or had an inadequate response to ruxolitinib.

Study design1

  • Three different doses of zinpentraxin alfa were evaluated for 9 cycles (36 weeks) in 97 patients:
    • 0.3 mg/kg Q4W
    • 3 mg/kg Q4W
    • 10 mg/kg Q4W
  • Patients without disease progression or discontinuation then proceeded to receive zinpentraxin alfa at 10 mg/kg in an extension study.
  • The primary endpoint was the BM response rate, defined by a ≥1-grade reduction in BM fibrosis based on the European Consensus criteria.
  • Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), hemoglobin, and platelet improvement were also assessed.

Key findings1

Efficacy

  • In total, 28.9% of patients experienced a BM response which was consistent across subgroups (Figure 1).
  • A BM improvement of 2-grades was most commonly observed in the 0.3 mg/kg cohort at 6.1%.
  • Across the entire cohort:
    • a total of 34% had ≥50% reduction in MPN-SAF TSS at any time vs baseline; and
    • clinical improvement and stable disease were reported in 16.5% and 69.1%, respectively.
  • In the 0.3 mg/kg, 3 mg/kg, and 10 mg/kg cohorts, respectively:
    • Hemoglobin improvements were highest in the 3 mg/kg cohort  (15.2%, 15.6%, and 6.3%)
    • Platelet improvements were highest in the 10 mg/kg cohort; (27.3%, 34.4%, and 37.5%)

Figure 1. BM improvement by cohort*

BM, bone marrow.
*Adapted from Verstovsek, et al.1

Safety

  • All patients experienced ≥1 treatment-emergent adverse events (TEAE), and 21.2% led to treatment discontinuation.
  • The most common serious TEAE across the whole study population were pneumonia (5.2%) and epistaxis (3.1%)
  • Grade 3–4 TEAE were most commonly observed in patients receiving 3 mg/kg compared with 0.3 mg/kg and 10 mg/kg (56.3% vs 36.4% and 37.5%)

Key learnings

  • Zinpentraxin alfa improved BM fibrosis, other hematologic parameters, and symptoms in patients with difficult-to-treat MF.
  • It is important to note that this trial had a small sample size and no control arm which limits conclusions to the efficacy of the intervention in isolation; therefore, further study is required.

References

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