By Rob Dillard
June 2, 2023
Patients with myelofibrosis (MF) with a certain platelet (PLT) count who achieve spleen volume reduction (SVR) on pacritinib have notably better overall survival (OS), according to a study presented at the 2023 American Society of Clinical Oncology Annual Meeting. That association was not observed in patients taking best available therapy (BAT).
One of the characteristics of MF is splenomegaly, or spleen enlargement. JAK2 inhibitors have been known to reduce spleen volume, which is considered a surrogate for disease response. Investigators, led by Helen Ajufo, MD, noted that ≥10% SVR on ruxolitinib is associated with improved OS among patients with PLT counts ≥100×109/L, and ruxolitinib cannot be administered at full dose in patients with a lower PLT count. Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has shown SVR benefit versus BAT. This study analyzed SVR and OS in patients from the PERSIST-2 trial.
Researchers assessed PERSIST-2 patients on pacritinib who were alive and treated at the start of the 12-week SVR window (study week 10) on pacritinib 200 mg BID or BAT. Spleen volume was assessed radiographically, OS was analyzed using various SVR thresholds (≥35%, ≥20%, ≥10%, and >0%), and OS was compared using the log-rank test.
Results showed that among patients on pacritinib (n=89), any SVR at 12 weeks was notably linked with improved survival (hazard ratio [HR], 0.08; 95% CI, 0.01-0.51, P=.0007). Across all SVR response thresholds, SVR ≥10% showed the greatest separation in OS curves between responders and nonresponders on pacritinib, with no deaths among 65 responders versus 5 deaths among 24 nonresponders (HR, 0.0; 95% CI, 0.0-0.14; P<.0001). By contrast, the investigators noted, SVR did not predict OS benefit on BAT (n=84), including ruxolitinib (n=39).
“In MF patients with PLTs ≤100×109/L, achieving SVR on full-dose [pacritinib] was associated with significant OS benefit. By contrast, this association was not found with BAT, even though most responders were on [ruxolitinib], albeit at low doses,” the researchers concluded. “As [pacritinib] can be given at full dose regardless of PLT count, it is possible that [pacritinib] may offer a unique survival advantage for MF patients with moderate or severe thrombocytopenia who achieve spleen reduction.”
Source: Ajufo H, Bewersdorf JP, Harrison C, et al. Spleen volume reduction (SVR) predicts overall survival (OS) in myelofibrosis (MF) patients on pacritinib (PAC) but not best available therapy (BAT): PERSIST-2 landmark OS analysis. Abstract #7018. Published for the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois.