ASCO 2015: JAK Inhibitor Pacritinib Proves Effective for Easing Symptoms of Myelofibrosis


Key Points

  • The JAK inhibitor pacritinib is significantly more effective than best available therapy for easing the symptoms of myelofibrosis.
  • At 24 weeks of treatment, 19.1% of patients on the pacritinib arm experienced > 35% spleen volume reduction vs 4.7% of patients on the best available therapy arm, and the majority of patients receiving pacritinib had some reduction in spleen size.
  • There was a significant reduction in the total symptomatic burden in patients receiving pacritinib. 

Findings from the PERSIST-1 study of patients with myelofibrosis show that the JAK inhibitor pacritinib is significantly more effective than best available therapy, which includes a range of off-label treatments, for easing the symptoms of myelofibrosis. At a landmark analysis at 24 weeks of treatment, 19.1% of patients on the pacritinib arm experienced a ≥ 35% spleen volume reduction, compared to only 4.7% of patients on the best available therapy arm.

“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, Arizona.  “We were encouraged to see that pacritinib was safe and effective in the trial, even in patients with severely low blood counts.” Dr. Mesa discussed the study at a press conference at the 2015 ASCO Annual Meeting and later during an oral session of leukemia, myelodysplasia, and transplantation (Abstract LBA7006).

Can Transform to Acute Myeloid Leukemia

About 20,000 people are affected by myelofibrosis in the United States. This chronic myeloid neoplasm “can impact patients with both significant morbidity in terms of splenomegaly symptoms and cytopenias as well as lead to mortality through a variety of difficulties,” Dr. Mesa explained at the press conference. “These individuals can have difficult symptoms, which can have a significant negative impact on their quality of life through a variety of mechanisms—everything from fatigue and night sweats to bone pain, fevers, and severe itching.” 

Thrombocytopenia in particular is a negative prognostic factor, “as well as a predictor of transformation to acute myeloid leukemia,” Dr. Mesa added. “The limitations in our therapy for myelofibrosis have been that we have not had agents that are able to simultaneously improve the splenomegaly and symptoms with which patients are afflicted while also impacting the cytopenias in a favorable way.”

Reduction in Spleen Volume, Platelet Counts

In the PERSIST-1 study, 327 patients were randomly assigned 2:1 to treatment with pacritinib (220 patients) or best available therapy (107 patients). Patients in the best available therapy group received therapies that are routinely prescribed off-label for myelofibrosis. These included erythropoietin-stimulating agents, immunomodulatory drugs such as thalidomide (Thalomid) and lenalidomide (Revlimid), and hydroxyurea. Ruxolitinib (Jakafi) was intentionally excluded because this study included patients with very low platelet counts, and ruxolitinib is not considered safe for those patients.

“The majority of patients receiving pacritinib had a reduction in spleen size,” Dr. Mesa noted, although not at the endpoint of ≥ 35% spleen volume reduction. “But many individuals have evidence of benefit at other levels,” he said. The degree of benefit in the best available therapy arm, Dr. Mesa noted, “is very modest.”

In the subgroup of patients with the lowest platelet counts (< 50,000/mL) and not candidates for any current therapy, 33.3% in the pacritinib group had spleen shrinkage, but no patients in the best available therapy group responded.

Compared with patients who had < 10% reduction in spleen volume, those achieving a spleen reduction between 10% and 20% and those above 20% had favorable hazard ratios, “highlighting the importance of splenic reduction in impacting the outcomes of these patients. We did not see such a favorable impact from the best alternative therapy arm,” Dr. Mesa noted.

Patients receiving pacritinib had “a significant reduction in the total symptom score, which is our aggregate tool for assessing the symptomatic burden in these patients,” Dr. Mesa explained. “A significantly higher proportion of patients became red cell transfusion–independent. Patients with baseline platelets < 50,000/μL had a mean increase in platelet counts of 35% by week 24,” Dr. Mesa added.

Longer Follow-up Needed

The most common side effects of pacritinib were diarrhea, nausea, and vomiting. The symptoms typically lasted less than 1 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, since it does not cause low platelet counts.

This study received funding from CTI BioPharma Corp. Dr. Mesa reported honoraria from Novartis Healthcare A/S; consulting or advisory roles with Novartis Healthcare A/S; and research funding from Incyte, Gilead Sciences, Celgene, and CTI. For full disclosures of the study authors, view the study abstract at

Watch The ASCO Post Evening News for an interview with Dr. Mesa recorded live at the 2015 ASCO Annual Meeting.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.