Spleen Volume Reduction Associated With Survival Benefit Among Patients With Myelofibrosis Receiving Pacritinib

Retrospective Analysis of the PERSIST-2 Trial

According to an analysis of the PERSIST-2 trial published in the Journal of Clinical Oncology, achieving spleen volume reduction (SVR) predicted overall survival (OS) outcomes among patients with myelofibrosis (MF) receiving pacritinib, but not among those receiving best available therapy (BAT). 

Janus kinase inhibitor (JAK)2 inhibitors, such as ruxolitinib, have been effective in reducing spleen volume, but “cannot be administered at full dose in patients with lower [platelets] (PLTs), and it is not known whether the association between SVR and OS persists in such patients,” according to Helen Ajufo, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors.

Pacritinib is a JAK1-sparing inhibitor of JAK2/interleukin-1 receptor-associated kinase 1 (IRAK1)/activin A receptor type 1 (ACVR1), which “demonstrated SVR benefit vs BAT (including [ruxolitinib]) in PERSIST-2, which enrolled MF patients with PLTs ≤100×109/L,” the study authors stated. 

This analysis is a retrospective landmark OS examination of the relationship between SVR and OS in the PERSIST-2 trial, which includes patients from this study who were alive at the start of the 12-week SVR window, or study week 10. These patients received pacritinib at 200 mg twice daily, or BAT. Assessments of spleen volume were conducted radiographically, through magnetic resonance imaging (MRI) or computed tomography (CT). OS was evaluated among SVR responders compared with non-responders within each group using different SVR thresholds, including ≥35%, ≥20%, ≥10%, and > 0%, as well as a landmark analysis methodology. A log-rank test was used to compare OS between groups. 

Results indicated that any SVR (> 0%) at 12 weeks was significantly correlated with improved survival among patients on pacritinib. Among all SVR thresholds, SVR ≥10% showed the largest separation in OS curves between responders versus non-responders who received pacritinib, with 0 deaths among 65 responders compared to 5 deaths among 24 non-responders. 

Conversely, SVR did not hold value in predicting OS benefit among patients who received BAT, including ruxolitinib (n = 39). Among patients who received BAT, 11% (n = 3) who achieved SVR ≥10% experienced mortality compared to 14% (n = 8) of non-responders. 

Dr Ajufo et al concluded, “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.”

“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,” they added. 

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. J Clin Oncol. Published online May 31, 2023. doi: 10.1200/JCO.2023.41.16_suppl.7018