At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Pankit Vachhani, MD, O’Neal Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama, presented a retrospective analysis of the PERSIST-2 and PAC203 studies. The analysis demonstrated that platelet count improvement meeting International Working Group (IWG) criteria occurred in a subset of patients with myelofibrosis (MF) treated with pacritinib, and does not seem to be explained by changes in spleen volume. 

Vachhani and coauthors noted that further studies are warranted to evaluate a connection between hematologic improvement and bone marrow fibrosis reduction among patients treated with pacritinib.

Transcript:

I am Pankit Vachhani, a leukemia physician at the University of Alabama at Birmingham. My colleagues and I presented a poster on December 11th, 2023 at ASH in San Diego on the platelet response in pacritinib-treated patients with cytopenic myelofibrosis. We know that thrombocytopenia is both prognostic of poor outcomes and also predictive of treatment intolerance with the currently available JAK1, JAK2 inhibitors like ruxolitinib. Pacritinib, on the other hand, is a JAK1-sparing inhibitor that's a JAK2, IDAC-1, and ACVR-1 inhibitor.This drug can be administered at full dose to patients irrespective of their baseline platelet count. All that's said and done, what we do not know from all the prior studies is what is the incidence of patients who have a platelet improvement when they receive treatment with pacritinib or other JAK inhibitors for that matter? We know that pacritinib can be dosed and leads to platelet stability, but what is the fraction of patients who improve their platelet counts? And that is what we wanted to study.

We included patients who had baseline platelet counts of less than 100 or [equal to]100 on the pacritinib 200 milligrams twice daily arms of the phase 3 PERSIST-2 study, and also the phase 2 PAC203 study. Patients who received best available therapy in the PERSIST-2 study were also included as a competitor arm. Our goal was to look into the platelet improvement. To that end, we used the hematologic improvement of platelet, in particular, that definition from the [International Working Group] (IWG) criteria. What that meant was for those patients with a baseline platelet count of less than 20, a platelet improvement was considered as one where the increase was to more than 20 and by at least 100%. While for those with a baseline platelet count of 2200, there should be at least an absolute increase of 30 on the platelet counts parameter.

No platelet transfusions should be sustained over any 8 weeks while on treatment. Overall, 117 patients were found in the pacritinib cohort [and]75 from the PERSIST-2 study, 42 from the PAC203 studies.Among the platelet responders in the pacritinib arm, 32% of the patients were ruxolitinib-naïve,while the rest had prior exposure to ruxolitinib at a median dose of about 10 milligrams twice daily. All put together, 16% of patients achieved a platelet improvement as defined by the criteria. That's on the pacritinib arm. For the best available therapy arm, only 5% of patients achieved the platelet improvement, so a marked difference between the 2 arms. There was no difference in terms of the magnitude of spleen volume or symptom score reduction that was observed in the platelet responders versus the non-responders in the pacritinib arm. The patients who saw a platelet count improvement with pacritinib saw that rather rapidly within the first few weeks, while those who did not see a platelet count improvement had more or less stable platelet counts.

The platelet count improvement in patients without recent [ruxolitinib] exposure was also looked into because there was a question of whether prior [ruxolitinib] use or its discontinuation may have led to a platelet count improvement for pacritinib-treated patients. Turned out that both the prior [ruxolitinib] exposed or not exposed patients saw improvements in platelet counts.

Finally, what we also noted was that those patients who got pacritinib and had a platelet response also happened to have bone marrow fibrosis reduction. The numbers were small, but there was an interesting signal that we noted there. Overall, there was no difference in the rate of bleeding events in platelet responders versus non-responders. The grade 3 or more bleeding events were observed at lower frequency in platelet responders compared to non-responders. To put it all together as a conclusion for pacritinib-treated patients, a 16% platelet count improvement incidence was noted in the PERSIST-2 and PAC203 study patients. We need to further assess the correlation between the hematologic improvement and bone marrow fibrosis. Turned out that the platelet count improvement in pacritinib-treated patients could not be explained just by improvements in spleen volume. One wonders whether pacritinib's JAK1's spreading activity and also IDAC-1 inhibition at the same time may be causing the modulation of bone marrow of microenvironment and therefore leading to a favorable thrombopoiesis in such patients. Thank you.

Source:

Vachhani P, Yacoub A, Traer E, et al. Platelet response in pacritinib-treated patients with cytopenic myelofibrosis: a retrospective analysis of PERSIST-2 and PAC203 studies. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 4554