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Pacritinib improves symptom control, reduces spleen volume in patients with myelofibrosis
CHICAGO — Pacritinib more effectively induced sustained spleen volume reduction and symptom control in patients with myelofibrosis compared with best available treatment, according to the results of a phase 3 trial presented at the ASCO Annual Meeting.
“Patients with myelofibrosis can have difficult symptoms which can have a significant negative impact on their quality of life,” Ruben A. Mesa, MD, professor of medicine at the Mayo Clinic in Scottsdale, Arizona, said during a press conference. “In our therapies for myelofibrosis, we have not had agents which have been able to simultaneously improve splenomegaly symptoms from which patients suffer while also impacting, in a favorable way, their cytopenias.”
Ruben A. Mesa
Myelofibrosis is a rare blood cancer that often results in spleen enlargement, according to a press release. Only one treatment — ruxolitinib (Jakafi, Incyte) — is FDA approved for this indication, but it is unsafe for patients with low blood platelet counts.
Pacritinib (CTI BioPharma) is an oral tyrosine kinase inhibitor that inhibits JAK2 without inhibiting JAK1, according to study background. In early-phase studies, treatment with pacritinib resulted in minimal myelosuppression.
Mesa and colleagues evaluated data from 327 patients (median time from diagnosis, 1.12 years) with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Thirty-two percent of patients had platelet counts less than 100,000 /µL and 15% had platelet counts less than 50,000/µL.
Researchers randomly assigned patients 2:1 to receive daily oral pacritinib (n = 220) or best available treatment (n = 107), which included erythropoietin stimulating agents, immunomodulatory drugs and hydroxyurea. Researchers excluded ruxolitinib as a treatment due to the risks associated with its use among patients with low platelet counts.
Spleen volume reduction of 35% or greater at 24 weeks in the intent-to-treat population served as the primary endpoint. A 50% or greater reduction of total symptom score at 24 weeks served as a secondary endpoint.
Median treatment duration was 16.2 months among patients assigned pacritinib and 5.9 months among patients assigned best available treatment.
Researchers observed statistically significant reductions in spleen volume at 24 weeks among patients in the pacritinib arm compared with patients in the best available therapy arm in the intent-to-treat population (19.1% vs. 4.7%; P = .0003) and the evaluable population (25% vs. 5.9%; P = .0001).
Seventy-nine percent of patients in the best available treatment arm crossed over to the pacritinib arm, and 21% had achieved targeted spleen reduction at data cutoff.
Researchers observed significantly higher composite total symptom score response rates in both the intent-to-treat population (24.5% vs. 6.5%; P < .0001) and the evaluable population
(40.9% vs. 9.9%; P < .0001).
Patients with baseline cytopenias also demonstrated benefit with pacritinib. In the intent-to-treat population, the rates for spleen volume reduction in the pacritinib vs. best available therapy arms were 16.7% vs. 0% (P = .009) among patients with platelet counts less than 100,000 /µL and 22.9% vs. 0% (P = .045) for patients with platelet counts less than 50,000/µL.
A total of 25.7% of red blood cell transfusion-dependent patients became transfusion independent after treatment with pacritinib, compared with no patients who received best available therapy (P = .043).
Researchers observed similar hematologic adverse events between both groups. Diarrhea, nausea and vomiting were the most commonly reported adverse events among patients assigned pacritinib.
“There is a significant greater proportion of patients achieving a response with pacritinib therapy regardless of platelet count,” Mesa said. “The significant treatment effect is particularly notable among high-risk patients, for whom no previous therapy was available.” – by Cameron Kelsall
Reference:
Mesa RA, et al. Abstract LBA7006. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: The study was funded by CTI BioPharma Corp. Mesa reports honoraria and researching funding from and consultant roles with Celgene, CTI, Gilead Sciences, Incyte and Novartis Healthcare A/S. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Myelofibrosis is a disease with only one approved agent. Pacritinib appears to result in significant symptomatic relief and reduction of transfusion requirements. The advantage pacritinib packed over the available other JAK2 inhibitor is that it can be used in patients with low counts. This is certainly a disease which can benefit from novel agents. It will be interesting to see that OS will be impacted after longer follow up or if it is active in patients previously exposed to the other JAK2 inhibitor ruxolitinib.