Parsaclisib Added to Ruxolitinib Decreases Spleen Volume and Improves Symptom Scores in Myelofibrosis

Kyle Doherty

The PI3Kδ inhibitor parsaclisib added to a stable dose of ruxolitinib (Jakafi) reduced spleen volume and improved symptom scores for patients with myelofibrosis who experienced a suboptimal response to ruxolitinib, according to findings from a phase 2 study (NCT02718300) published in Blood Adv.

Final results of the study revealed that patients who received daily-to-weekly dosing of parsaclisib (n = 32) and those who received all-daily dosing of parsaclisib (n = 42) achieved a decrease in spleen volume of at least 10% at 12 weeks at rates of 28.0% and 59.5%, respectively. Moreover, patients achieved a 50% decrease or more at week 12 in Myelofibrosis Symptom Assessment Form symptom scores at rates of 14% and 28%, respectively; the rates of at least a 50% decrease at week 12 in Myeloproliferative Neoplasms Symptom Assessment Form symptom scores were 18% and 32%, respectively.

“Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the PI3K/protein kinase B pathway,” Abdulraheem Yacoub, MD, professor of Hematologic Malignancies and Cellular Therapeutics at KU Medical Center in Kansas City, Kansas, and coauthors wrote. “The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib.”

The study authors added that parsaclisib was designed with a different molecular structure than earlier-generation PI3K inhibitors—the orally bioavailable, potent, and highly selective next-generation inhibitor may in turn be able to limit both on- and off-target toxicities that were previously seen.

Additional findings from the study demonstrated that in the overall population evaluable for the primary end point (n = 65), the median change in spleen volume was −163.6 cm3 (range, −735.6 to 10173 cm3), with a median percentage change of −11% (range, −47% to 444%). At week 24, these figures were −192.0 cm3 (range, −2040 to 761.4 cm3) and −10% (range, −89% to 34%) among 49 evaluable patients. The median percentage change was greater among patients who received all-daily dosing compared with those who received daily-to-weekly dosing both at 12 weeks (−15.0% vs −2.0%) and 24 weeks (−19.0% vs −2.5%, respectively).

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Addition of Parsaclisib to Ruxolitinib Decreases Spleen Volume and Improves Symptom Scores Among Patients With Myelofibrosis

Jordan Kadish

02/23/2024

The addition of parsaclisib to stable-dose ruxolitinib treatment decreased spleen volume, improved symptom scores, and yielded acceptable safety among patients with primary or secondary myelofibrosis (MF), according to findings from a phase 2 trial published in Blood Advances.

Abdulraheem Yacoub, MD, The University of Kansas Cancer Center, Kansas City, Kansas, and coauthors explained that although ruxolitinib has demonstrated beneficial results among patients with intermediate- or high-risk myelofibrosis, “suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway.”

In this phase 2 trial, the study authors aimed to measure the potential benefit of adding PI3Kδ inhibitor parsaclisib to ruxolitinib treatment among patients with primary or secondary myelofibrosis who did not have optimal responses to ruxolitinib alone. The primary end points were dosing, efficacy, and safety of this treatment combination.

All patients included in this study stayed on a stable dose of ruxolitinib. Among these patients, 32 were administered parsaclisib at 10 or 20 mg once daily for 8 weeks, then once weekly afterward (daily-to-weekly dosing). Additionally, 42 patients were administered parsaclisib at 5 or 20 mg once daily for 8 weeks, and then 5 mg once daily afterward (all-daily dosing).

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