Imatinib Mesylate Therapy for Patients (pts) with Polycythemia Vera (PV).

Imatinib is a potent inhibitor of tyrosine kinases, including abl, c-kit, and platelet-derived growth factor receptor (PDGFR). A role for PDGF in PV has been suspected, and direct inhibition of PV colonies with imatinib has been reported. We initiated a phase II trial of imatinib in pts with PV diagnosed by the Polycythemia Vera Study Group criteria. Pts were treated with imatinib at 400 mg daily; if no significant response after 1 month (mo) of therapy, the dose could be escalated to 800 mg daily. Hydroxyurea could be used only during the first mo of therapy, but anagrelide was allowed at any time. 9 patients have been treated (6 male, 3 female). Median age was 51 years (yrs) (range 28 to 72 yrs); median duration of PV was 8 years (range 1/4–35 years). ECOG performance status was 0 for 2 pts and 1 for 7 pts. Most common symptoms included fatigue (n=7), intractable pruritus (n=5) and headache (n=4). 4 pts had splenomegaly, 1 had hepatomegaly, and 1 had prior splenectomy. All patients were dependent on repeated phlebotomies. All pts had diploid cytogenetics except one who had 20q⁻ (prior therapy with ³² P). FISH and PCR confirmed absence of Bcr-Abl translocation.

After a median follow-up of 4 mo (range, 2 to 37 mo), 3 pts have ≥50% reduction in phlebotomy requirements. These include one pt with complete remission defined as hemoglobin < 14 g/dl, no phlebotomies and complete resolution of splenomegaly. Pruritus improved significantly in 3 pts; fatigue improved in 3 pts, headache and visual symptoms improved in one pt each. The dose of imatinib was increased to 800 mg in 3 pts. Grade 3 diarrhea and liver dysfunction occurred in 1 pt requiring dose reduction to 300 mg daily. Grade 2 toxicities included edema (n=2), rash (n=1), bone pain (n=1) and diarrhea (n=1). We conclude that imatinib has activity in PV, leading to improved symptoms and decreased phlebotomy requirements.