Imatinib Mesylate for Patients (pts) with Hypereosinophilic Syndrome (HES) and Systemic Mastocytosis (SM): A Phase II Trial.

Imatinib is a potent inhibitor of the tyrosine kinases c-abl, c-kit, ARG, platelet-derived growth factor (PDGFR)-alpha and PDGFR-beta. We and others have reported on the clinical efficacy of imatinib in pts with HES and SM. We report here on 28 pts (16 HES, 12 SM) treated in a phase II study of imatinib. Pts with HES received imatinib at a starting dose of 100 mg daily with escalation to 400 mg if no response after 1 month (mo). Pts with SM were started at a dose of 400 mg with possible escalation to 800 mg. The median age was 52 years (yrs) (26–77 yrs). All pts had signs and symptoms of end-organ involvement with 10 (83%) of 12 pts with SM having skin involvement. 15 (53%) of 28 pts had received prior therapies. Imatinib was started within 34 mo from diagnosis (3–162 mo). Prior to the start of imatinib, the median eosinophil count for pts with HES was 2.2 x10⁹/L (0.5–7 x10⁹/L) and the median percentage of eosinophils in the bone marrow was 19% (5%–28%). 2 of the pts with SM had increased eosinophils, 9 pts have been evaluated for serum tryptase level; this was increased in 5 (0 HES, 5 SM). 6/16 (37%) pts with HES responded: 3 achieved a complete remission (CR) (defined by the disappearance of eosinophilia and signs and symptoms of disease) and 3 a partial response (PR) (defined by the reduction of eosinophilia and organomegaly by > 50%). Two pts (1 CR, 1 PR) required dose escalation to 400 mg. The median duration of response was 11+ mo (1+ to 21+). One patient died in CR at 18 mo, 1 was lost to follow-up after 1 mo in CR; 2 have ongoing response (1 PR, 1 CR) 15+ and 21+ mo, respectively; and 2 lost PR after 3 and 10 mo, respectively despite dose escalation. 7/12 pts with SM (58%) responded. Six pts achieved a major response (MR) (defined by the complete resolution of at least one clinical finding and no progression in other clinical findings): 4 CRs, 1 PR (defined by the incomplete regression of one or more clinical finding(s) without complete regression and without progress in other clinical findings) (Leuk Res 27:635,2003). One pt (MR) required imatinib escalation to 800 mg. The median duration of response was 14+ mo (7+ to 36+). At the time of response, 2 pts had normalized their tryptase levels. Only one pt has lost response (PR) after 9 mo. Overall, treatment was well tolerated. 2 pts experienced grade 3 diarrhea; one of them required imatinib dose reduction. We conclude that therapy with imatinib for patients with HES and SM appears effective and well tolerated.