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Parsaclisib in patients with MF and suboptimal ruxolitinib response

May 10, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in myelofibrosis.

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Intermediate- or high-risk myelofibrosis (MF) can be treated with ruxolitinib to reduce spleen size, manage symptoms, and increase survival.1 However, many patients have a suboptimal response to ruxolitinib or relapse over time. Therefore, treatments for post-ruxolitinib failure are currently under investigation.

Here, we summarize a phase II study by Yacoub et al.1 published in Blood Advances which investigates the addition of parsaclisib, a phosphoinositide 3-kinase inhibitor, for patients with MF who responded suboptimally to initial ruxolitinib treatment.

Study design1

  • This study consisted of four parts:
    • Part one investigated a tolerable dose of parsaclisib after ruxolitinib.
    • Parts two to four investigated the efficacy and safety of different parsaclisib dosing schedules.
  • Eligible patients had received ruxolitinib ≥6 months at a dose of 525 mg twice daily for 8 weeks prior to the study start, with suboptimal response.
  •  The primary endpoints included:
    • Part one: Determining a well-tolerated dose of parsaclisib in combination with ruxolitinib according to MF Symptom Assessment Form Scores (MFSAF).
    • Part two to four: Absolute change and percentage change in spleen volume from baseline to Week 12.
  • After the maximum and minimum doses had been investigated, patients were regrouped and randomized to either daily or daily to weekly parsaclisib dosing schedules (Figure 1).

Figure 1. Study design*  

QD, once daily; QW, once weekly; Rux, ruxolitinib.
*Adapted from Yacoub, et al.1 Created with 

Key findings1

  • Overall, 74 patients were enrolled across all parts of the study.
  • Baseline characteristics were similar between groups, with a median age of 68 years and 47% male.
  • In part one:
    • The maximum tolerated dose of parsaclisib was 20 mg daily.
    • No dose-limiting toxicities were reported.
    • 96% of patients experienced ≥1 treatment-emergent adverse event and nausea was most reported (23%).
  • In parts two to four:
    • 88% of patients were evaluable for the primary endpoint of absolute change.
    • Percentage change in spleen volume from baseline to Week 12, with the remaining patients not evaluable due to discontinuation.
    • Among those who met the primary endpoint, the median percentage change of spleen volume from baseline to Week 12 was −11% (Figure 2).
    • The median percentage change was greatest in patients receiving daily doses of parsaclisib compared with weekly.

Figure 2. Median percentage change of spleen volume from baseline, Week 12, and Week 24 in patients treated daily and weekly with parsaclisib after ruxolitinib treatment*

SV, spleen volume.
*Adapted from Yacoub, et al.1

  • In a spleen volume reduction analysis from baseline to Week 12, 46% of patients achieved spleen volume reductions ≥10%;
    • Patients who received daily doses of parsaclisib reported higher spleen volume reductions ≥10% than those who received daily-to-weekly dosing (59.5% vs 28%).
  • Median percentage change in MFSAF from baseline to Week 12 was −20.5%;
    • Daily doses of parsaclisib produced a higher MFSAF percentage change than daily weekly doses (−33% vs −14%).

Key learnings 

  • Parsaclisib treatment after suboptimal ruxolitinib response reduced splenomegaly and improved symptoms in patients with MF.
  • Patients who received daily parsaclisib dosing after ruxolitinib treatment achieved larger decreases in spleen volume and symptom scores according to MFSAF compared with patients receiving daily-to-weekly dosing.
  • These findings suggest that the addition of parsaclisib to ruxolitinib therapy may improve outcomes for patients with MF, especially when administered daily.

  1. Yacoub A, Borate U, Rampal R, et al. Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results. Blood Adv. 2024;8(6):1515-1528. DOI: 1182/bloodadvances.2023011620


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