Pacritinib Exhibits Consistent Efficacy for Spleen and Symptom Response Among Patients With Myelofibrosis, Regardless of Cytopenias

Pacritinib, a novel Janus kinase 1 (JAK1)-sparing inhibitor of JAK2/interleukin-1 receptor-associated kinase 1 (IRAK1)/activin A receptor type 1 (ACVR1), demonstrated consistent efficacy for spleen and symptom response among patients with myelofibrosis (MF), regardless of cytopenias. 

According to Prithviraj Bose, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors, “Unfortunately, dosing – and thus efficacy – of available current JAK1/2 inhibitors is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias.” Therefore, there is a need for data on therapies for patients with myelofibrosis across the cytopenic spectrum. 

In this study, Dr Bose et al aimed to assess the efficacy of pacritinib on spleen and symptom benefit among patients with myelofibrosis across the cytopenic spectrum. A total of 276 patients who received pacritinib in the PERSIST-1 and PERSIST-2 studies and were evaluable for spleen response were stratified by baseline platelet (PLT) count (<100, ≥100x109/L) and hemoglobin (HB) levels (<8, 8 to <10, ≥10 g/dL). Patients were then analyzed for depth of spleen volume response (SVR), modified total symptom score (TSS) response, patient global impression of change (PGIC), and dose intensity.

Among all evaluable patients, 51.5% had grade 3 fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. The median dose intensity was >99.7% across PLT and HB subgroups. Notably, 80% of patients had ≥10% SVR (SVR-10), 75.5% had TSS-10, and 78% stated that their symptoms improved at week 24. Spleen reduction at week 24 was consistent across PLT and HB groups, with 84% to 93% of patients in the PLT group experiencing spleen reduction, compared with 86% to 90% in the HB group. 

SVR ≥35% was observed in 23% to 25% of patients across the PLT group and in 21% to 28% of patients across the HB group. Symptom response was comparable across groups, except for TSS-50, which occurred at the highest rate of 62.5% among patients with HB <8 g/dL. There was no reduction in symptom burden among patients with thrombocytopenia. Across subgroups, ≥ 75% of patients reported that their symptoms were “improved” at week 24. 

Dr Bose et al concluded, “Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts.”
“This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias,” they added. 

Source: 

Bose P, Gagelmann N, Gupta V, et al. Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias. J Clin Oncol. Published online May 31, 2023. doi: 10.1200/JCO.2023.41.16_suppl.7068