Imatinib Mesylate (GLEEVEC®) Is Effective in the Treatment of Polycythemia Vera: A Multi-Institutional Clinical Trial.

We previously reported that the erythrocytosis of polycythemia vera was controlled in a small group of patients with imatinib mesylate. This effect may involve inhibition of tyrosine phosphorylation of c-Kit, the stem cell factor receptor essential for erythroid progenitor cell proliferation. We now report treating 27 polycythemia vera patients with imatinib in a multi-institutional study. There were 13 men, 14 women, median age 52 years, range 29 to 83 yrs. All had an increased 51Cr RBC mass determination at diagnosis and fulfilled stipulated criteria for the diagnosis of polycythemia vera. Sixteen of 27 had platelets counts greater than 400,000/?l. Prior to imatinib, disease duration ranged from 1 month to 15 years (median 31 months, mean 52.1 months). Eleven patients had been treated only by phlebotomy; 16 with hydroxyurea, interferon, or anagrelide and supplemental phlebotomy. Men were initially phlebotomized to a hematocrit of 45% or less and women to a hematocrit of 42% or less. Prior to imatinib, the average number of phlebotomies per year ranged from 0 to 14 (median 6); after 1 yr of imatinib, phlebotomy number ranged from 0 to 6 (median 1). Imatinib was started at 400 mg qd escalating every 2 weeks by 100 mg to a maximum of 800 mg for persistent phlebotomy requirements or for platelet counts above 400,000/?l. All patients received 81 mg of aspirin daily. There were 5 complete remissions (CR) (phlebotomy-free, normal platelets, no splenomegaly) and 8 partial remissions (PR) (phlebotomy-free but platelet counts greater than 400,000?/l and/or splenomegaly). No patient with initial thrombocytosis achieved a platelet count less than 400,000/?l with imatinib. Four patients are too early to evaluate. Of the remaining 10, there were 2 failures (one developed myelofibrosis, one increasing thrombocytosis and a TIA but no neurologic sequelae), one protocol violation and 2 patients were removed for unrelated medical conditions. Five of these 10 patients developed drug toxicity: grade 3 dermatologic (n=2); grade 3 diarrhea (n=2); grade 3 bone pain (n=1); all recovered with drug withdrawal. The mean time to CR/PR was 4 months. The median duration on treatment was 11 months. Thus, of 23 evaluable patients to date, 13 (57%) have had a CR or PR. The difference in response of thrombocytosis in CML patients to imatinib compared to polycythemia vera is notable and requires further evaluation. We conclude that imatinib is useful for treating erythrocytosis and controlling splenomegaly in some patients with polycythemia vera, but not for controlling thrombocytosis or splenomegaly in others. These data suggest heterogeneity of the mechanisms involved in hematopoietic stem cell proliferation in PV or patient variability with respect to the metabolism of imatinib.