Pacritinib Proves Feasible as Pretransplant Bridge Therapy in Myelofibrosis

Data from the HOVON134MF trial (NCT03645824) showed that pacritinib (Vonjo; CTI BioPharma), a targeted therapy for myelofibrosis (MF), can safely and effectively prepare high-risk patients for allogeneic stem cell transplantation—the only known cure for the disease—without preventing them from reaching that critical treatment milestone.

Why Pacritinib?

Current EBMT (formerly European Society for Blood and Marrow Transplantation) guidelines recommend Janus kinase (JAK) inhibitor therapy before transplant to reduce spleen size and improve symptoms, as responding patients tend to have better transplant outcomes. However, older agents such as ruxolitinib (Jakafi; Incyte Corporation) can cause significant drops in blood counts, which is a significant concern in patients already dealing with the cytopenias common in advanced MF.

Pacritinib is a next-generation JAK2/IRAK1/ACVR1 inhibitor that spares JAK1, giving it a more favorable blood count profile. HOVON-134 was specifically designed to evaluate whether this drug could fill an unmet clinical need in transplant-eligible patients—a population that had been excluded from previous landmark JAK-inhibitor trials.

What the Trial Found

The prospective, multicenter, phase 2 study enrolled 61 patients with intermediate-2 or high-risk MF between 2018 and 2022. All participants intended to proceed to allogeneic hematopoietic stem cell transplantation (alloHSCT), and most were able to.

Patients received pacritinib at 200 mg twice daily for three to four 28-day cycles before proceeding to transplant. The results were encouraging on multiple fronts.

Symptom response, defined as a 50% or greater reduction in total symptom score, was achieved in 36% of patients. Among the 46 patients with baseline enlarged spleens, 43% achieved a meaningful reduction in spleen size. Blood counts remained stable throughout treatment, reinforcing pacritinib's tolerability profile.

Regarding safety, 44% of patients experienced at least one grade 3 or 4 adverse event during treatment, well below the prespecified feasibility threshold of 70%. Gastrointestinal adverse effects were the most common concern, though severe cases were rare and manageable. Notably, there were low rates of cardiac events and no serious bleeding complications.

Most strikingly, 95% of enrolled patients successfully proceeded to transplant, surpassing the trial's benchmark of 80%. Two patients died before transplant: 1 from a neurological complication of their underlying disease and 1 during conditioning from an undetermined cause.

Longer-Term Outcomes

With a median follow-up of nearly 5 years, overall survival at 1 year was 80% and at 5 years was 57%. Nonrelapse mortality at 5 years post transplant was 25%, with causes including infection, graft-vs-host disease, and other complications. Among patients transplanted under protocol, no primary graft failures occurred.

The Bottom Line

HOVON-134 offers meaningful evidence that pacritinib is a viable bridge to transplant for high-risk myelofibrosis patients, including those with low blood counts who may not tolerate other JAK inhibitors. As the authors note, it may be particularly relevant for cytopenic patients, and a future randomized trial comparing pacritinib to ruxolitinib in the pretransplant setting could help define its place in therapy more precisely.

REFERENCES

1. Myelofibrosis treated with pacritinib before aSCT. (HOVON134MF) (HOVON134MF). Clinicaltrials.gov. Updated August 22, 2022. Accesed April 9, 2026. https://clinicaltrials.gov/study/NCT03645824

2. Van Dijck R, van der Holt B, Broers AEC, et al. Pacritinib in transplant-eligible myelofibrosis: final analysis of the phase II HOVON-134 trial. Bone Marrow Transplant. March 18, 2026. Doi:10.1038/s41409-026-02841-0