Retrospective Data Show Pacritinib Improves TSS in Transfusion-Dependent Myelofibrosis

Pacritinib (Vonjo) demonstrated significant symptom improvement compared with best available therapy (BAT) in patients with myelofibrosis who required red blood cell (RBC) transfusions at baseline, according to data from a retrospective analysis of the phase 3 PERSIST-2 trial (NCT02055781) presented at the 2024 ASCO Annual Meeting.¹

Findings showed that 31% of transfusion-dependent patients treated with pacritinib (n = 35) achieved at least a 50% reduction in total symptom score (TSS) vs 9% for those given BAT (n = 34; P =.034). The BAT group included patients treated with low-dose ruxolitinib (Jakafi; n = 13), and 15% of these patients experienced at least a 50% TSS reduction.

Further analysis in patients with a baseline platelet count of less than 50 × 10⁹/L showed that pacritinib (n = 21) reduced TSS score by at least 50% in 24% of patients compared with 10% for BAT (n = 20) and 11% for ruxolitinib (n = 9).

“This retrospective analysis shows that pacritinib provides substantial symptom benefit compared with BAT or low-dose ruxolitinib, specifically in patients who require RBC transfusion,” lead study author Stephen T. Oh, MD, PhD, and colleagues wrote in a poster presentation of the data. Oh is an associate professor of medicine (hematology) and pathology & immunology and co-chief of the Division of Hematology at the Washington University School of Medicine in St. Louis, Missouri.

Study Design

PERSIST-2 was a randomized phase 3 study that evaluated pacritinib vs BAT in patients with myelofibrosis and thrombocytopenia.² Notably, prior findings from the study supported the February 2022 FDA accelerated approval of pacritinib for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10⁹/L.³

The retrospective analysis included patients who were not transfusion independent (TI) at baseline.¹ To be included, they needed to be randomly assigned to 1 of the 2 treatment arms at least 22 weeks prior to study termination and have a baseline platelet count of no more than 100 x 10⁹/L.

The primary objectives of the retrospective analysis were the rate of patients with at least a 50% reduction in TSS and Patient Global Impression of Change (PGIC) at week 24.

Baseline Patient Characteristics

Among patients included in the retrospective analysis, the median age was 67 years for the pacritinib group, 70 years for the BAT group, and 72 years for the ruxolitinib subgroup. Approximately half of patients were classified as high-risk by the Dynamic International Prognostic Scoring System in the pacritinib group (45.7%), the BAT group (50.0%), and the ruxolitinib subgroup (53.8%).

The median platelet counts were 45 x 10⁹/L in both pacritinib and BAT groups vs 43 x 10⁹/L for the ruxolitinib subgroup. The median hemoglobin levels were 8.5 g/dL in the pacritinib group, 8.7 g/dL in the BAT group, and 8.6 g/dL in the ruxolitinib subgroup.

At baseline, the median number of RBC transfusions required over the prior 90 days was 1.51 units per month in the pacritinib group, 1.71 units per month in the BAT group, and 1.7 units per month for the ruxolitinib group. More than half of the patients in each group had prior exposure to JAK2 inhibitors, including 57.1% in the pacritinib group, 52.9% in the BAT group, and 76.9% in the ruxolitinib subgroup.

Median spleen volume was similar across groups, measuring 2225.9 cm³ in the pacritinib group, 2120.6 cm³ in the BAT group, and 2451.6 cm³ in the ruxolitinib group. The median palpable spleen length was 16 cm in the pacritinib group and 11 cm in both the BAT and ruxolitinib groups.

Additional Efficacy and Safety Data

For spleen-related symptoms, patients treated with pacritinib achieved a median reduction of 51% compared with 4% for BAT and 25% for ruxolitinib. Similarly, cytokine-related symptoms were reduced by 62% with pacritinib vs a 15% increase with BAT; there was a 42% reduction in cytokine-related symptoms with ruxolitinib.

Although physical function symptoms were not included in TSS, these were improved with pacritinib. The median reduction was 33% for pacritinib compared with 9% for BAT and 17% for ruxolitinib. For fatigue specifically, pacritinib led to a 37% reduction vs 13% with BAT, and inactivity improved by 30% for pacritinib vs 4% for BAT.

Furthermore, PGIC data showed that 37% of patients in the pacritinib group reported a significant improvement in symptoms at week 24 compared with 9% of patients on BAT (P = .009) and 8% of those on ruxolitinib.

Among the 11 patients treated with pacritinib who experienced at least a 50% reduction in TSS, 6 patients (54.5%) also achieved a TI response compared none of the TSS responders treated with BAT.

Furthermore, individual symptom reductions were more substantial among TI responders on pacritinib compared with non-responders. These symptoms included tiredness (49.5% reduction for TI responders vs 35.0% for TI non-responders), inactivity (33.0% vs 28.5%), early satiety (46.0% vs 44.0%), abdominal discomfort (50.0% vs 38.5%), left rib pain (97.0% vs 60.5%), night sweats (86.5% vs 30.0%), itching (73.0% vs 0%), and bone pain (48.5% vs 12.5%).

Grade 3 or higher anemia that was deemed a treatment-emergent adverse effect (TEAE) occurred in 17.1% of patients treated with pacritinib vs 16.5% of patients given BAT. Fatigue TEAEs were reported in 14.6% of patients on pacritinib vs 14.0% on BAT. In the experimental arm, no instances of grade 3 or higher fatigue occurred, and fatigue did not lead to any dose modifications. Two patients (4.7%) in the BAT arm experienced grade 3 or higher fatigue that was deemed a TEAE, and fatigue led to a dose reduction in 1 patient (2.3%) in this arm.

References

1. Oh S, McCloskey JK, Sobas M, et al. Impact of pacritinib on symptoms in with thrombocytopenia and myelofibrosis who require red blood cell transfusion. J Clin Oncol. 2024;42(suppl 16):6577. doi:10.1200/jco.2024.42.16_suppl.6577
2. Pacritinib versus best available therapy to treat patients with myelofibrosis and thrombocytopenia (PAC326). ClinicalTrials.gov. Updated November 18, 2021. Accessed November 12, 2024. https://clinicaltrials.gov/study/NCT02055781
3. CTI BioPharma announces FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. CTI BioPharma Corp. News release. February 28, 2022. Accessed November 12, 2024. https://www.prnewswire.com/news-releases/cti-biopharma-announces-fda-accelerated-approval-of-vonjo-pacritinib-for-the-treatment-of-adult-patients-with-myelofibrosis-and-thrombocytopenia-301492159.html