Comprehending the full value of ruxolitinib for polycythemia vera (PV) and myelofibrosis (MF) patients is critical for its wider use in daily clinical practice, according to a review published in the SOHO 2019 Meeting Proceedings Supplement in Clinical Lymphoma, Myeloma and Leukemia.
PV typically presents with increased erythroid counts, low serum erythropoietin levels, sometimes splenomegaly, and a higher risk of thrombotic and microvascular events compared with MF, which typically presents with increased bone marrow fibrosis, cytopenia’s, progressive hepatosplenomegaly, extramedullary hematopoiesis, constitutional symptoms, such as night sweats, fever, and weight loss, as well as an increased risk for leukemic transformation.
The Janus kinase (JAK)1/2 inhibitor ruxolitinib is FDA approved for the treatment of intermediate and high-risk MF and for the treatment of PV in patients who have an inadequate response or intolerance to hydroxyurea. This dual JAK1/JAK2 oral inhibitor possesses a half-life of 3 hours and is metabolized by CYP34A and mostly eliminated by urine excretion.
Ruxolitinib’s exhibited safety and efficacy in the phase III COMFORT-1 and COMFORT-2 trials, with a primary endpoint of more than 35% spleen volume reduction (SVR), and secondary endpoint of symptomatic improvement by 50%. Ruxolitinib was correlated with a decrease in cytokine levels, and this drop resulted in an improvement in symptoms. Despite these improvements, ruxolitinib has a marginal effect on bone marrow fibrosis, and allogeneic hematopoietic stem cell transplant (allo-HCT) remains the only curative therapy. In patients experiencing failing hydroxyurea, two phase III trials demonstrated a higher spleen volume reduction, hematocrit control and total symptom score in patients treated with ruxolitinib versus standard of care.
The authors concluded that “ruxolitinib has significantly changed the management of patients with polycythemia vera in second line setting, leading to improvements in symptom control/quality of life, hematocrit, WBC and platelet control, splenomegaly reduction, and apparent decrease in thromboembolic events.”
They added that understanding the “full value of ruxolitinib for PV patients not responding well to hydroxyurea is of outmost importance for its wider utility in everyday practice.”