Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hyperosinophilic syndrome - a phase-II study

Metzgeroth, G., Walz, C., Erben, P., Popp, H., Schmitt-Graeff, A., Haferlach, C., Fabarius, A., Schmittger, S., Grimwade, D., Cross, N.C., Hehlmann, R., Hochhaus, A. and Reiter, A. (2008) Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hyperosinophilic syndrome - a phase-II study. British Journal of Haematology, 143 (5), 707-715. (doi:10.1111/j.1365-2141.2008.07294.x).

Abstract

This study evaluated the efficacy and safety of imatinib in chronic eosinophilic leukaemia (CEL, n = 23) and hypereosinophilic syndrome (HES, n = 13). In CEL with FIP1L1-PDGFRA (n = 16) or various PDGFRB fusion genes (n = 5), complete haematological remission (CHR) was achieved in 95% (20/21) after 3 months. Complete molecular remission (CMR) was seen in 75% (12/16) of cases with FIP1L1-PDGFRA positive CEL by 6 months, and in 87% (13/15) after 12 months. CMR was achieved in three of five PDGFRB fusion positive patients after 3, 9 and 18 months respectively. All patients are currently on imatinib (100 mg; n = 13, 400 mg; n = 8) and no molecular relapse has yet been observed (median 26·7 months; range, 6·9–39·9). Imatinib was less effective in HES and CEL without known molecular aberration (n = 15); CHR was observed in 40% (6/15) of patients, two patients relapsed after 4·8 and 24·5 months. Three patients died due to imatinib-resistant progressive CEL (n = 2) or myocardial infarction (n = 1) unrelated to study treatment. Overall, imatinib was well tolerated with a low incidence of grade III/IV toxicities. These data confirmed the long-term efficacy of imatinib for PDGFR-rearranged CEL patients, and also showed that a minority of HES cases without known molecular aberrations may benefit from imatinib.

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Contributors

Author: N.C. Cross

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