Imatinib mesylate is effective in the treatment of polycythemia vera: A multi-institutional clinical trial

Abstract

6532 Background: We previously reported that the erythrocytosis of polycythemia vera (PV) was controlled with imatinib mesylate in a cohort of patients. This effect may involve inhibition of tyrosine phosphorylation of c-Kit, the stem cell factor receptor essential for erythroid progenitor cell proliferation. Methods: We report treating an expanded cohort of 37 PV patients with imatinib in a multi-institutional phase II trial. All patients had an increased 51Cr RBC mass determination at diagnosis and fulfilled the stipulated criteria for the diagnosis of PV. Men were initially phlebotomized to a hematocrit (HCT) ≤ 45%; women to HCT ≤ 42%. Imatinib was started at 400 mg qd escalating 100 mg every 2 weeks to a maximum of 800 mg for persistent phlebotomy (PHL) requirements or for platelet counts > 600 × 109/L. All patients received 81 mg of aspirin qd. Results: There were 21 men, 16 women, median age 51 years, range 29–83. Prior to imatinib, mean disease duration was 60.2 mos; average number of PHLs per year ranged from 0–23 (mean=9). After 1 year of imatinib, PHLs ranged from 0 to 9 (mean=2). There were 9 complete remissions (PHL-free, platelets ≤ 600 × 109/L, no splenomegaly) and 10 partial remissions (PHL and/or splenomegaly decreased by 50% of initial values with platelets ≤ 600 × 109/L, or platelets > 600 × 109/L but no PHL requirements or splenomegaly); 1 patient, protocol violation. Thus, of 36 evaluable patients, 19 (53%) responded. Of the remaining 17, 10 failed due to disease progression: myelofibrosis (n=2); platelets > 1,000 × 109/L with PHL and/or splenomegaly (n=2); repeated PHLs (n=1); cytogenetic abnormalities (n=1); increasing thrombocytosis (n=1); and a TIA (n=1). Seven of 17 with no remission developed toxicity: grade 3 dermatologic (n=2); grade 3 diarrhea (n=2); grade 3 bone pain (n=1), liver (n=1); heart failure (n=1). Median treatment duration: 17.2 months. Conclusions: We conclude that imatinib is useful for treating erythrocytosis and controlling splenomegaly in a significant proportion of PV patients, but is less effective for controlling thrombocytosis or splenomegaly in others. These data suggest heterogeneity of hematopoietic stem cell proliferation in PV or patient variability with respect to imatinib metabolism. [Table: see text]