Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia

Abstract

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ("much" or "very much" improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.

Trial registration: ClinicalTrials.gov NCT02055781 NCT04884191.

Figures

Figure 1.

Efficacy of pacritinib versus best available therapy based on 24-week response rates in patients with severe thrombocytopenia. Graph depicts the percentage of patients achieving ≥35% spleen volume reduction (SVR), achieving ≥50% reduction in modified Total Symptom Score (TSS), and reporting symptoms as being “much” or “very much” improved based on Patient Global Impression of Change (PGIC) at week 24. Percentages are based on all patients randomized at least 22 weeks prior to the termination of the PERSIST studies (intention-to-treat [ITT] population). BAT: best available therapy; CI: confidence interval; PAC: pacritinib.

Figure 2.

Waterfall plots of percentage change from baseline. (A) Change in spleen volume and (B) change in modified Total Symptom Score (TSS) at week 24 in patients with severe thrombocytopenia. Data are shown for evaluable patients treated with pacritinib (pooled dose groups) or best available therapy (BAT) (including ruxolitinib, indicated with red asterisks). Gray horizontal lines indicate responder threshold (35% for spleen volume reduction [SVR], 50% for TSS).

Figure 3.

Self-reported symptoms in patients who completed the Patient Global Impression of Change at week 24 by treatment group. The percentage of evaluable patients with any improvement in disease symptoms was higher for patients randomized to pacritinib (84% [47/56]) than for those randomized to best available therapy (BAT) (48% [10/21]).

Figure 4.

Median hemoglobin and platelet count over time through week 24. Among patients remaining on study, the median hemoglobin (A) and platelet count (B) remained stable over time in both pacritinib- and best available therapy (BAT)-treated patients. IQR: interquartile range.