Achieving a spleen volume reduction of at least 10% on a full dose of pacritinib was associated with significant overall survival (OS) benefits in patients with myelofibrosis who have moderate or severe thrombocytopenia.
Jan Philipp Bewersdorf, MD, of the Memorial Sloan Kettering Cancer Center, and colleagues conducted the research and presented their findings during the 2023 European Hematology Association Congress.
Pacritinib previously demonstrated a spleen volume reduction benefit compared with the best available therapy in the PERSIST-2 trial, which included patients who had myelofibrosis and platelet counts of ≤100×109/L.
Dr. Bewersdorf and colleagues evaluated patients enrolled in PERSIST-2 who were alive and participating in the study at the start of a 12-week assessment window for spleen volume reduction. Patients received pacritinib 200 mg twice a day or best available therapy. The researchers compared OS outcomes between patients who had a spleen volume reduction response and those who did not have a response in each treatment arm.
They analyzed multiple thresholds for spleen volume reduction, including reductions of at least 35%, at least 20%, at least 10%, and more than 0%. Among all the thresholds they analyzed, the spleen volume reduction of at least 10% showed the greatest separation in OS between patients who responded to pacritinib (n=65) and those who did not respond (n=24).
“Interestingly, while [a spleen volume reduction of at least 35%] is considered to be the threshold for spleen response in myelofibrosis studies, this was a less predictive indicator of survival on [pacritinib] … as many patients with a [a spleen volume reduction of less than 35%] were long-term survivors,” Dr. Bewersdorf and colleagues wrote.
There were no subsequent deaths among patients who responded, while five of the patients who did not respond died (hazard ratio, 0.0; 95% CI, 0.0-0.14; P<.0001). A spleen volume reduction of more than 0% and a spleen volume reduction of at least 20% at week 12 were both associated with “improved survival” although separation of the response curves was “not as great,” according to Dr. Bewersdorf and colleagues.
However, in contrast to the results observed with pacritinib, achieving a spleen volume reduction on the best available therapy (n=84) was not associated with improved survival, regardless of the spleen volume reduction threshold. Of the 28 patients receiving best available therapy who achieved a spleen volume reduction of at least 10%, 82% received ruxolitinib. Of those patients, most were receiving a low dose of ruxolitinib at the time of the landmark analysis, while the median relative dose intensity on pacritinib was 100% through week 12 among patients who responded and those who did not.
“In myelofibrosis patients with moderate and severe thrombocytopenia, achieving ≥10% [spleen volume reduction] on full-dose [pacritinib] was associated with significant OS benefit,” Dr. Bewersdorf and colleagues concluded. “By contrast, this association was not found with [the best available therapy], even though most responders were on [ruxolitinib], albeit at low doses. As [pacritinib] can be given at full dose regardless of platelet count, it is possible that [pacritinib] may offer a unique survival advantage for myelofibrosis patients with moderate or severe thrombocytopenia who achieve spleen reduction.”
Bewersdorf J, Ajufo H, Harrison C, et al. Spleen volume reduction predicts survival in myelofibrosis patients on pacritinib but not best available therapy: PERSIST-2 landmark overall survival analysis. Abstract P1030. Presented at the 2023 European Hematology Association Congress. June 8-15. 2023; Frankfurt, Germany.