A phase II trial of imatinib in patients with refractory/relapsed myeloma.
Although imatinib was designed to specifically inhibit the bcr-abl gene product, it inhibits other receptor tyrosine kinases including c-kit. As pre-clinical data, 126 patients with plasma cell disorders and 19 controls were evaluated for c-kit expression. Patients were eligible for the treatment trial if they had relapsed/refractory myeloma. The primary end-point of the study was response. Of the 145 studied before the trial, c-kit expression was present on the bone marrow plasma cells of control (11%), AL amyloid (53%), MGUS (47%), SMM (67%) and MM (42%) patients. Twenty-three MM patients were enrolled on the therapeutic trial (imatinib 400 mg daily) and 52% had positive c-kit staining. There were no responses. The median duration of treatment was 48 days (range: 12-349). Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imatinib is not an active agent in patients with relapsed or refractory multiple myeloma.
Dispenzieri
Angela
A
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA. dispenzieri.angela@mayo.edu
Gertz
Morie A
MA
Lacy
Martha Q
MQ
Geyer
Susan M
SM
Greipp
Phillip R
PR
Rajkumar
S Vincent
SV
Kimlinger
Teresa
T
Lust
John A
JA
Fonseca
Rafael
R
Allred
Jacob
J
Witzig
Thomas E
TE
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor