A phase II trial of imatinib in patients with refractory/relapsed myeloma

Area of Science:

• Oncology
• Pharmacology
• Hematology

Background:

• Imatinib inhibits bcr-abl and other receptor tyrosine kinases, including c-kit.
• C-kit expression is found in various plasma cell disorders, including multiple myeloma (MM).

Purpose of the Study:

• To evaluate the efficacy of imatinib in patients with relapsed or refractory multiple myeloma.
• To assess the role of c-kit expression in predicting response to imatinib therapy.

Main Methods:

• Pre-clinical evaluation of c-kit expression in 126 patients with plasma cell disorders and 19 controls.
• A therapeutic trial involving 23 MM patients with relapsed/refractory disease treated with imatinib 400 mg daily.
• Primary endpoint was treatment response; median treatment duration was 48 days.

Main Results:

• C-kit expression varied across plasma cell disorders: controls (11%), AL amyloid (53%), MGUS (47%), SMM (67%), and MM (42%).
• Of 23 MM patients treated, 52% had positive c-kit staining.
• No responses were observed; treatment was discontinued due to disease progression (18), death (3), or other reasons (2).

Conclusions:

• Imatinib demonstrated no therapeutic activity in patients with relapsed or refractory multiple myeloma.
• C-kit expression in MM plasma cells does not appear to predict response to imatinib therapy.