Pacritinib for spleen volume reduction prior to allo-HSCT in patients with cytopenic MF

Splenomegaly poses a higher risk of delayed engraftment, poor graft function, and non-relapse mortality following allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients with myelofibrosis (MF).¹ JAK1/2 inhibitors such as ruxolitinib and fedratinib may be used to reduce spleen volume and thereby improve post-transplant outcomes.

However, dosing of these agents is limited in cytopenic patients with MF. Pacritinib is approved by the U.S. Food and Drug Administration (FDA) for adults with MF and a platelet count of <50 × 10⁹/L, indicating potential use for spleen volume reduction in cytopenic patients.¹

At the 49th Annual Meeting of the EBMT, Nico Gagelmann presented a poster highlighting data from the phase III PERSIST-2 trial on the efficacy of pacritinib for spleen volume reduction in patients with MF across the cytopenic spectrum.¹ The MPN Hub is pleased to summarize key data from this presentation.

Study design

A total of 57 patients treated with pacritinib 200 mg twice daily (BID) were evaluated for spleen volume reduction over 24 weeks, stratified by baseline blood counts:

• Platelet count: <50 × 10⁹/L and 50 to <100 × 10⁹/L
• Hemoglobin: <8 g/dL, 8 to <10 g/dL, and ≥10 g/dL           

Initial baseline characteristics are outlined in Table 1.

Table 1. Baseline patient and disease characteristics*

BID, twice daily; JAK, Janus kinase. *Adapted from Gagelmann, et al.1
Characteristic, % (unless otherwise stated)	Pacritinib 200 mg BID (N = 57)
Median age, years	67
Primary myelofibrosis	75
Prior JAK inhibitor	42
Median palpable spleen length, cm (below left costal margin)	14
Baseline platelet count <50 × 109/L	37
Baseline platelet count 50 to <100 × 109/L	42
Baseline hemoglobulin <8 g/dL	18
Baseline hemoglobulin 8 to <10 g/dL	37
Baseline hemoglobulin ≥10 g/dL	46

Results

• Patient data were categorized by spleen volume reduction >35% (SVR35), 25%, 10%, and >0% by baseline platelet count. However, any spleen reduction (>0%) was defined as a clinical improvement.
• A clinical improvement was recorded in 80–91% of patients, regardless of cytopenia. Overall results are outlined in Table 2.

Table 2. Overall spleen volume reduction regardless of cytopenia*

*Data from Gagelmann, et al.1
Spleen volume reduction, %	Overall response (N = 57)
>35%	28
>25%	40
>10%	79
>0%	84

All platelet subgroups achieved an overall spleen volume reduction by the end of Week 12 and maintained a stable median platelet count. Patients with a baseline platelet count of <50 × 10⁹/L achieved the highest rate of spleen volume reduction, with 45% achieving SVR35.

Conclusion

The use of pacritinib to reduce spleen volume was shown to be effective in patients with MF across the cytopenic spectrum. However, the degree of efficacy was influenced by baseline platelet count, with patients with a count of <50 × 10⁹/L achieving the highest rates of SVR35. Data from PERSIST-2 support the use of pacritinib prior to allo-HSCT to reduce splenomegaly and mitigate the risk of its related poor outcomes and may be particularly beneficial in patients with cytopenic MF.