Parsaclisib Added to Ruxolitinib for Myelofibrosis Improves Symptoms and Spleen Volume

By Keightley Amen - Last Updated: December 12, 2022

Final data from a phase II study indicate that adding parsaclisib can improve symptoms and spleen volume in patients with myelofibrosis (MF) who have had a less than optimal response to ruxolitinib. The results were presented at the 2022 American Society of Hematology Annual Meeting.

Although Janus kinase (JAK) inhibitor ruxolitinib has been shown to be safe and effective against MF, “suboptimal or declining responses to ruxolitinib occur in a subset of patients, possibly due to persistent PI3K pathway activation with chronic JAK inhibitor therapy,” wrote the authors, led by Abdulraheem Yacoub, MD, of the University of Kansas Cancer Center in Westwood, Kansas. Their study sought to test the safety and efficacy of adding PI3Kδ inhibitor parsaclisib.

The study included patients with MF who had a suboptimal response, defined by splenomegaly and symptomatology, despite six or more months of ruxolitinib treatment. The patients continued ruxolitinib and were randomized to receive:

  • Parsaclisib 10 mg or 20 mg once daily for eight weeks and the same dose once weekly thereafter (QD/QW group, n=32)
  • Parsaclisib 5 mg or 20 mg daily for eight weeks and 5 mg daily thereafter (all QD group, n=42)

Median treatment duration was 336.5 days. Overall, patients showed improvements in symptoms and spleen volume. Notably, the “all QD” regimen was more effective than QD/QW.

Adverse events related to treatment were mostly grade 1 or 2 and included pneumonia (n=5), fatigue (n=2), hypoxia (n=2), dyspnea (n=2), fall (n=2), increased alanine aminotransferase (n=2), increased aspartate aminotransferase (n=2), and hypocalcemia (n=2).

Grade 3 thrombocytopenia occurred in 17 patients, and grade 4 thrombocytopenia occurred in nine. Adverse events led to parsaclisib interruption in about 50% of patients and ruxolitinib interruption in less than 20%. They led to parsaclisib discontinuation in 12% and ruxolitinib discontinuation in 5%. Other reasons for discontinuation included rollover into an open-label parsaclisib trial and progressive disease.

Phase III research is in progress.


Yacoub A, Borate U, Rampal RK, et al. Efficacy and safety of add-on parsaclisib to ruxolitinib therapy in myelofibrosis patients with suboptimal response to ruxolitinib: final results from a phase 2 study. Abstract #236. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.

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