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Published on: December 7, 2014

Add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: a randomized phase 3 study

Jean-Jacques Kiladjian1, Uma Borate2, Elisabetta Abruzzese3

  • 1Saint-Louis Hospital, Paris Cité University, INSERM, Paris 75010, France.

The Oncologist
|May 25, 2026
PubMed
Abstract

Insights

Adding parsaclisib to ruxolitinib did not significantly improve outcomes for myelofibrosis patients, showing no meaningful clinical benefit. Further research into combination therapies is warranted for this patient population.

Area of Science:

  • Hematology
  • Oncology
  • Pharmacology

Background:

  • Myelofibrosis is a serious condition often treated with ruxolitinib, a JAK1/JAK2 inhibitor.
  • Some patients do not respond well to ruxolitinib due to persistent PI3K/AKT pathway activation.
  • Parsaclisib, a PI3Kδ inhibitor, was investigated as an add-on therapy.

Purpose of the Study:

  • To evaluate the efficacy and safety of adding parsaclisib to ruxolitinib in myelofibrosis patients with suboptimal response.
  • To assess spleen volume reduction and symptom score changes in patients receiving the combination therapy versus placebo.

Main Methods:

  • A phase 3, randomized, double-blind, placebo-controlled study (LIMBER-304) was conducted.
  • Eligible patients had primary or secondary myelofibrosis, received ruxolitinib, had a palpable spleen, and a high symptom score (MFSAF TSS ≥10).
  • Primary endpoint was spleen volume reduction (≥25%) at 24 weeks; key secondary endpoint was symptom score reduction (≥50%).

Main Results:

  • 16.7% of patients on parsaclisib/ruxolitinib achieved ≥25% spleen volume reduction versus 9.7% on placebo/ruxolitinib (not statistically significant).
  • ≥50% reduction in total symptom score was observed in 17.1% with parsaclisib/ruxolitinib versus 14.1% with placebo/ruxolitinib.
  • Higher rates of infections and gastrointestinal disorders were noted with parsaclisib/ruxolitinib, and the study was terminated early due to efficacy findings.

Conclusions:

  • Adding parsaclisib to stable ruxolitinib therapy is unlikely to provide significant clinical benefits for myelofibrosis patients.
  • The combination therapy showed increased adverse events, including serious infections.
  • Further investigation into JAK and PI3K inhibitor combinations is needed for effective myelofibrosis treatment.
Keywords:
parsaclisibprimary myelofibrosisruxolitinibspleen

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