Update: Ruxolitinib Beats Best Available Therapy in Treating Polycythemia Vera

An updated meta-analysis confirms that ruxolitinib, the Janus kinase (JAK) 1/JAK2 inhibitor sold as Jakafi, offers improvements in key measures of efficacy compared with best available therapy (BAT) for patients with polycythemia vera (PV),¹ a rare, slow-progressing disorder that causes the blood to make too many red blood cells.

Caused by a genetic mutation, PV is not typically fatal on its own, but it can cause dangerous blood clots and damage to the spleen. In a small number of cases, it progresses to more aggressive forms of blood cancer.

The latest results were reported in the journal APMIS,¹ formerly known as Acta Pathologica, Microbiologica, et Immunologica Scandinavica.

The analysis followed a 2020 meta-analysis involving 16 studies that appeared in Blood Advances.² That analysis included evidence from 4 randomized controlled trials and included 663 patients; the authors estimated a thrombosis incidence of 3.09% per year for ruxolitinib vs 5.51% for BAT, but noted that globally, this did not reach significance (P = .098). “A clinical trial on selected patients at high risk of thrombosis would be warranted, but its feasibility is questionable,” the authors wrote.²

The current analysis examines ruxolitinib’s efficacy and safety compared BAT in 1061 patients with PV and in hydroxyurea-resistant and intolerant patients with PV across 6 studies, with a cutoff of November 2023. The patients included 620 on BAT and 441 on ruxolitinib. According to the investigators:

• Those taking ruxolitinib showed higher hematocrit control (P = .015) and treatment response (P = .04) compared to BAT.
• Patients taking ruxolitinib had significantly improved Myeloproliferative Neoplasms-Symptom Assessment Form scores (MPN-SAF), P < .01.

However, on the safety front, patients with PV treated with ruxolitinib had higher rates of nonmelanoma skin cancer (P < .01), as has been previously documented.

Subgroup analyses that detailed results for those patients who were resistant or intolerant to hydroxyurea showed that ruxolitinib maintained its efficacy; the therapy significantly improved responses (P < .01) and also demonstrated improvements in the MPN-SAF (P = 0.02) score when compared to BAT.

Investigators reported that the safety findings were consistent with the overall results:

• Ruxolitinib showed significantly reduced thromboembolism rates (P = .04)
• Investigators reported increased rates of anemia (P = .01), and increased herpes zoster infections (P = .02)

Investigators concluded, “Ruxolitinib outperforms BAT in PV and patients with PV-resistant or intolerant to hydroxyurea, offering better hematocrit control and reducing symptomatic burden and thromboembolism risk. Yet, it is associated with higher rates of anemia, herpes infection, and skin cancer.”¹

References

1. Mora MMR, Afzal F, Guimaraes CR, et al. Efficacy and safety of ruxolitinib vs best available therapy for polycythemia vera: An updated systematic review and meta-analysis. APMIS. Published online October 8, 2024. doi: 10.1111/apm.13472.
2. Masciulli A, Ferrari A, Carobbio A, Ghirardi A, Barbui T. Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis. Blood Adv. 2020;4(2):380-386. doi: 10.1182/bloodadvances.2019001158.