Study backs Vonjo use for myelofibrosis as safe step before transplant
Therapy eased symptoms; most patients were able to undergo procedure
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A magnifying glass is surrounded by a scattering of pills. (Photo by iStock)
Treatment with Vonjo (pacritinib) before a stem cell transplant safely eased symptoms and spleen enlargement in people with myelofibrosis, while also allowing most patients to undergo their planned procedure, according to final findings from a Phase 2 trial.
The findings support Vonjo as a “feasible and effective symptomatic treatment” for transplant-eligible patients, researchers wrote, while noting that “its pre-transplant use” does not limit patients’ ability to proceed to their intended transplant.
The study, “Pacritinib in transplant-eligible myelofibrosis: final analysis of the phase II HOVON-134 trial,” was published in the journal Bone Marrow Transplantation.
Vonjo targets key protein
Myelofibrosis is a rare blood cancer marked by the buildup of scar tissue in the bone marrow, the spongy tissue inside bones where blood cells are made. As a result, the production of healthy blood cells is impaired, leading to cytopenia (low blood cell counts) and other symptoms. As the spleen tries to compensate by producing blood cells, people may also develop splenomegaly, or an enlarged spleen.
An allogeneic stem cell transplant, also known as allogeneic hematopoietic stem cell transplantation (alloHSCT), is currently the only potentially curative treatment for myelofibrosis. The procedure involves providing the body with donor blood-forming stem cells to repopulate the bone marrow with healthy blood cells. Because the whole process can be intensive, it is usually reserved for people with high-risk disease who are fit enough to undergo the procedure.
Current guidelines recommend the use of JAK inhibitors as a standard first-line treatment for intermediate- or high-risk myelofibrosis before transplant to help reduce spleen enlargement and ease symptoms such as fever, fatigue, night sweats, and bone pain.
Among these therapies is Vonjo, a JAK inhibitor marketed by Sobi that primarily targets JAK2, a protein linked to abnormal cell growth and inflammation. Unlike some other drugs in the same class that also inhibit JAK1 and may worsen low platelet counts, Vonjo is designed to avoid that effect and may also help reduce inflammation and anemia. However, data on the use of newer JAK inhibitors such as Vonjo in the pre-transplant setting remain limited, as transplant-eligible patients have largely been excluded from major clinical trials evaluating these therapies.
Treatment reduces spleen size by at least 50% in nearly half of patients
To address this knowledge gap, a team of researchers conducted a Phase 2 trial, HOVON-134 (NCT03645824), between July 2018 and February 2022. The study involved 61 adults with intermediate or high-risk myelofibrosis who were considered eligible for and who intended to undergo a stem cell transplant.
Participants had a median age of 64, 69% were men, and 38% had previously been treated with the JAK inhibitor Jakafi (ruxolitinib). They received oral Vonjo at a dose of 200 mg twice daily for three to four 28-day cycles, depending on donor availability, and stopped treatment one day before starting conditioning therapy. The latter consists of a course of high-dose chemotherapy to eliminate abnormal bone marrow cells and make room for donor stem cells.
The study aimed to determine whether Vonjo could safely be used before transplant to reduce spleen volume and ease symptoms without preventing patients from moving forward with the planned alloHSCT.
Results showed that 36% of participants achieved a symptom response, defined as at least a 50% reduction in total symptom scores on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), a validated tool for evaluating symptoms. Among the 46 participants with splenomegaly (increased spleen size) at the start of the study, 43% achieved at least a 50% reduction in spleen size after treatment. The median time to spleen response was 48 days.
[Vonjo] is a feasible and effective symptomatic treatment in transplant-eligible [myelofibrosis] patients and its pre-transplant use does not limit higher-risk patients in proceeding to their intended alloHSCT.
Researchers also found that median levels of hemoglobin, a marker of anemia (low red blood cell count), and counts of platelets, which promote clotting, remained generally stable during treatment. According to the team, these findings suggest Vonjo may be particularly suitable as a pre-transplant treatment in patients with cytopenia.
Overall, 69% of participants remained on the 200 mg dose of Vonjo throughout the treatment period. Severe adverse events occurred in 44% of participants. Gastrointestinal side effects were the most common serious adverse events linked to Vonjo, affecting 8% of patients.
Among participants, 95% ultimately proceeded to stem cell transplant. Two patients died before transplant, one during Vonjo treatment due to a buildup of fluid in the brain linked to blood cell production outside the bone marrow, and one during conditioning therapy from a presumed neurological event.
Among transplanted patients, overall survival rates were 78% at one year and 60% at five years after transplant. The researchers noted that transplant outcomes were generally consistent with those previously reported with Jakafi in the same setting.
“[Vonjo] is a feasible and effective symptomatic treatment in transplant-eligible [myelofibrosis] patients and its pre-transplant use does not limit higher-risk patients in proceeding to their intended alloHSCT,” the researchers concluded. They added that future randomized controlled trials may help clarify how Vonjo compares with Jakafi in the pre-transplant setting.
