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

Findings from a Phase 2 Trial

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).

Study results indicated that 28% of patients in the daily-to-weekly dosing group achieved a ≥ 10% decrease in spleen volume at 12 weeks, compared to 59% of patients in the all-daily dosing group. Among the patients in the daily-to-weekly dosing group, a total of 14% achieved a ≥ 50% decrease at week 12 in Myelofibrosis Symptom

Assessment Form (MFSAF) symptom scores, and 18% achieved a ≥ 50% decrease at week 12 in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) symptom scores, compared to 28% and 32% of patients in the all-daily dosing group. 

In terms of safety, the most prevalent nonhematologic treatment-emergent adverse events were nausea, diarrhea, abdominal pain and fatigue, and cough and dyspnea. New-onset grade 3 and 4 thrombocytopenia occurred in 19% of patients in the daily-to-weekly dosing group, as well as 26% and 7% of patients in the all-daily dosing group, managed with dose interruption. The study authors noted that the hemoglobin levels among patients remained steady. 

Yacoub and coauthors concluded, “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.”

Source: 

Yacoub A, Borate U, Rampal RK, et al. Phase 2 study of add-on parsaclisib in myelofibrosis patients with suboptimal response to ruxolitinib: Final results. Blood Adv. Published online: January 30, 2024. doi: 10.1182/bloodadvances.2023011620