An ongoing subgroup analysis from a phase 2 trial of parsaclisib in patients with myelofibrosis (MF) and low platelet counts (PC) were presented at the 2021 Annual American Society of Hematology (ASH) Meeting.

“We previously demonstrated preliminary efficacy in a phase 2 trial of parsaclisib added to stable doses of ruxolitinib for patients with MF who experienced a suboptimal response. Janus kinase (JAK) inhibitors, including ruxolitinib, are associated with thrombocytopenia; therefore, patients with low PC are traditionally difficult to treat,” elaborated Abdulraheem Yacoub, MD, University of Kansas Cancer Center, Kansas, and co-investigators.

Patients eligible for enrollment had primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF with suboptimal response after 6 months or more of ruxolitinib monotherapy (5-25 mg twice daily, stable dose ≥8 weeks).

Further, patients remained on their last stable ruxolitinib dose and received add-on parsaclisib 10 mg or 20 mg once daily for 8 weeks and the same dose once-weekly thereafter, or parsaclisib 5 mg or 20 mg once daily for 8 weeks and 5 mg once daily thereafter.

“For the subgroup analysis, patients were grouped by baseline PC, either ≥100x10⁹/L, higher PC or 50-<100x10⁹/L, low PC,” continued Dr Yacoub and co-authors.

The primary endpoints were to evaluate the impact of baseline PC on spleen volume (SV) and total symptom score (TSS) as assessed by Myelofibrosis-Symptoms Assessment Form (MFSAF) v3.0 daily diary at week 12 and week 24, and safety.

In total, 67 patients were enrolled, 46 with high PC and 21 with lower PC. Baseline characteristics included the median age of both groups being 68 years old. The median duration of prior ruxolitinib treatment was 34.7 months for low PC and 14.9 months for higher PC.

Notably, patients with low PC had higher baseline symptoms (MFSAF-TSS median, 21.4 [0.6-47]) than patients with higher PC (MFSAF-TSS, 10 [0-43]).

“At week 12, slightly more patients with low PC achieved ≥ 10% SV reduction (SVR) compared to those with higher PC, whereas, at week 24, responses were similar between the 2 groups. Of patients with at least 10% SVR at week 24, 4 of 6 with low PC and 9 of 13 with higher PC were receiving all daily dose regimens,” explained Dr Yacoub and co-investigators.

Between both baseline PC groups, nonhematologic treatment-emergent adverse events (TEAEs) were mostly grade 1 or 2. Most common TEAEs in the low PC group were dyspnea (33%), falls (33%), peripheral edema (29%), and nasal congestion (24%). For the higher PC group, patients experienced diarrhea (28%), nausea (24%), abdominal pain (24%), and cough (20%).

Interruption of parsaclisib due to thrombocytopenia was observed in 9 of the 21 patients (43%) with low PC and 3 of the 46 patients (7%) with higher PC.

“In a subgroup analysis by baseline PC, responses for SV and MFSAF-TSS reduction were similar in both groups, indicating that patients with low PC can also tolerate and benefit from this treatment combo. Phase 3 trials in RUX-experienced and RUX-naïve patients are underway to further assess the combination of JAK and P13K inhibitors,” concluded Dr Yacoub, et al.—Alexa Stoia

Yacoub A, Borate U, Rampal R, et al. Subgroup Analysis from a Phase 2 Study of the Efficacy and Safety of Parsaclisib, a Selective P13Kδ Inhibitor, in Combination with Ruxolitinib in Patients with Myelofibrosis (MF). Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3647