Findings from the PERSIST-1 study of patients with myelofibrosis suggest that pacritinib is significantly more effective than best available therapy (BAT), which includes a range of off-label treatments.

At 24 weeks of treatment, 19.1% of patients on the pacritinib arm experienced spleen shrinkage, compared to only 4.7% of patients on the BAT arm.

Myelofibrosis is a rare blood cancer, and spleen enlargement is a common, debilitating symptom.

Pacritinib also improved a range of additional symptoms and eliminated the need for blood transfusion in a quarter of patients who had previously been dependent on transfusions due to low blood counts.

This experimental therapy was also beneficial for a subgroup of patients with very low blood platelet counts, for whom no FDA approved therapy exists.

“There is a huge unmet clinical need for patients with myelofibrosis. Only one drug is currently FDA approved for the disease, and it is not safe for patients with low platelet counts,” said lead study author Ruben A. Mesa, MD, Deputy Director of the Mayo Clinic Cancer Center in Scottsdale.

“We were encouraged to see that pacritinib was safe and effective in the trial, even in patients with severely low blood counts.”

About 20,000 people are affected by myelofibrosis in the United States.

The disease develops when the bone marrow does not make enough normal blood cells.

As a result, the spleen takes over blood cell production and becomes enlarged.

Patients also often experience tiredness, weakness, shortness of breath, fever, and weight loss.

In about a third of patients, myelofibrosis transforms into acute leukaemia.

There is currently no cure for myelofibrosis, besides allogeneic hematopoietic (bone marrow) stem cell transplant, which is an option that is not feasible for many, and the only FDA approved treatment is a JAK inhibitor, ruxolitinib.

Several other agents targeting JAK proteins are in development.

In the PERSIST-1, 327 patients were randomly assigned to treatment with pacritinib or BAT.

Patients on the BAT arm received therapies that are routinely prescribed off-label for myelofibrosis, such as erythropoietin stimulating agents, immunomodulatory drugs (e.g., thalidomide, lenalidomide), and hydroxyurea.

Ruxolitinib was intentionally excluded because this study included patients with very low platelet counts, for which this drug is not deemed to be safe.

The effects of pacritinib were seen as early as four weeks of starting treatment.

At 24 weeks, 19.1% of patients in the pacritinib arm had a reduction in spleen size, compared to only 4.7% in the BAT arm.

In the subgroup of patients with the lowest platelet counts (those who are not candidates for ruxolitinib), spleen shrinkage occurred in 33.3% of patients in the pacritinib arm and 0% in the BAT arm.

Compared to patients on the BAT arm, patients on the pacritinib arm experienced a greater degree of relief from symptoms such as cachexia (involuntary weight loss), night sweats, fever, and bone pain.

The vast majority (79%) of patients on the BAT arm eventually crossed over to the pacritinib arm.

Pacritinib also helped alleviate anaemia in some patients; among patients who had been dependent on red blood cell transfusion, 25.7% no longer needed the procedure.

In contrast, none of the patients on the BAT arm became transfusion independent.

The most common side effects of pacritinib were diarrhoea, nausea, and vomiting.

The symptoms typically lasted less than one week and few patients discontinued treatment due to side effects.

Longer follow up is needed to determine if pacritinib improves survival.

The ongoing PERSIST-2 phase III trial is exploring pacritinib for the treatment of patients who have low blood platelet counts due to their disease, or due to their therapy.

Dr. Mesa remarked that pacritinib may be an attractive agent to combine with other therapies, as it does not cause low platelet counts.

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Source: ASCO