Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study.

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.

• Authors: Georgia Metzgeroth, Christoph Walz, Philipp Erben, Helena Popp, Annette Schmitt-Graeff, Claudia Haferlach, Alice Fabarius, Susanne Schnittger, David Grimwade, Nicholas C P Cross, Rüdiger Hehlmann, Andreas Hochhaus, Andreas Reiter
• Journal: British journal of haematology (Br J Haematol) Vol. 143 Issue 5 Pg. 707-15 (Dec 2008) ISSN: 1365-2141 [Electronic] England
• PMID: 18950453 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Oncogene Proteins, Fusion
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• mRNA Cleavage and Polyadenylation Factors
• Imatinib Mesylate
• FIP1L1-PDGFRA fusion protein, human
• Receptor, Platelet-Derived Growth Factor alpha
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Adult
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Cytogenetics
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Hypereosinophilic Syndrome (drug therapy, genetics)
• Imatinib Mesylate
• Male
• Middle Aged
• Neoplasm, Residual
• Oncogene Proteins, Fusion (genetics)
• Piperazines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines (therapeutic use)
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Receptor, Platelet-Derived Growth Factor beta (genetics)
• Remission Induction (methods)
• Reverse Transcriptase Polymerase Chain Reaction
• Treatment Outcome
• mRNA Cleavage and Polyadenylation Factors (genetics)