Pacritinib Elicits Early Responses in Multi-Refractory Chronic Graft-Vs-Host Disease

Graft-vs-Host Disease |
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Pacritinib (Vonjo) demonstrated preliminary efficacy with an acceptable toxicity profile in patients with multi-refractory chronic graft-vs-host disease (cGVHD), according to data from a phase 1 study (NCT05531786) presented at the 51st Annual EBMT Meeting.1

At a median follow-up of 15 months (range, 8-20.3), the agent elicited an overall response rate (ORR) of 67% at 6 months, with 4 patients experiencing partial responses (PRs) and 2 achieving stable disease (SD). The treatment was found to be tolerable with no dose-limiting toxicities (DLTs) reported. Only 1 patient experienced grade 3 or higher arthralgia, which was not determined to be related to study treatment.

“Pacritinib, an oral CSF1R/JAK2/IRAK1 inhibitor, has shown a favorable safety profile with promising response rates in [patients with] multi-refractory severe cGVHD at the initial dose level,” Noa G. Holtzman, MD, of University of Miami Sylvester Cancer Center, in Florida, and colleagues, wrote in a poster. “Accrual for dose level 2 [DL2] is ongoing.”

Pacritinib targets CSF1R, JAK2, and IRAK1, which are important inflammatory and fibrotic pathways associated with GVHD pathophysiology. The agent received accelerated approval from the FDA in February 2022 for use in adult patients with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count under 50 × 109/L.2 Investigators hypothesized that pacritinib could potentially be an effective option against severe cGVHD—one that would not lead to dose-limiting cytopenias.1 To this end, they launched a phase 1 study to further explore this agent in this population.

The modified dose-escalation study, which was sponsored by the National Cancer Institute, enrolled patients with moderate or severe cGVHD who did not respond to at least 2 prior lines of systemic therapy.3 Patients were required to be at least 18 years of age, have a Karnofsky performance status of at least 60%, and have acceptable organ and bone marrow function.

Study participants received pacritinib at 100 mg twice daily (dose level 1; DL1) or 200 mg twice daily (DL2) on days 1 to 28 of a 28-day treatment cycle.1 Treatment continued for up to 1 year if PR or SD was achieved. Accrual to DL1 has been completed, and accrual for DL2 is still underway. Investigators monitored adverse effects (AEs) and conducted clinical response assessments after 6 weeks, and then 3, 6, 9, and 12 months of treatment in accordance with the 2014 National Institutes of Health cGVHD Response Criteria.

In phase 1, the primary objective was to determine the maximum tolerated dose after DLT. Secondary efficacy end points comprised 6-month ORR. Investigators also examined patient-reported outcomes (PROs). At the time of data cutoff, half of patients had completed 12 months of treatment.

At the time of data cutoff, 7 patients had been enrolled to the trial and 6 had received treatment. The mean patient age was 44 years (range, 27-69), and most patients were male (83%) and Caucasian (67%). The median time from hematopoietic stem cell transplantation (HSCT) to study enrollment was 5.4 years (range, 4.1-12.3), and the median time from cGVHD diagnosis to study enrollment was 3.4 years (range, 2.2-7.5). All patients had severe cGVHD with a median of 3 organs involved. The median prior number of therapies received was 6 (range, 2-9); all patients had received steroids, and 83% received ruxolitinib (Jakafi)/belumosudil (Rezurock).

With regard to PROs, 60% of patients were noted to have a meaningful decrease of 7 or more points in the Lee Symptom Scale.

In terms of safety, the most common grade 2 or higher AEs experienced at DL1 were upper respiratory infection (n = 5), dyspepsia (n = 2), abdominal pain, increased alanine and aspartate aminotransferase levels, infective conjunctivitis, dysgeusia, decreased ejection fraction, eye disorders, hypokalemia, and hypophosphatemia (n = 1, each).

“Treatment was tolerated well without any early treatment discontinuation or dose [reductions], and there have been no cases of relapse or death,” study authors concluded.

References

1. Holtzman NG, Mina A, Jurdi NE, et al. Phase 1 study of pacritinib, a CSF1R/JAK2/IRAK1 inhibitor, for refractory chronic graft-versus-host disease: A preliminary analysis. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract B057.
2. 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 April 2, 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
3. A phase I/II study of pacritinib, a JAK2/IRAK1/CSF1R inhibitor, in refractory chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). ClinicalTrials.gov. Updated March 25, 2025. Accessed April 2, 2025. https://clinicaltrials.gov/study/NCT05531786