Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.
In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.
Tefferi
Ayalew
A
Mayo Clinic, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
Mesa
Ruben A
RA
Gray
Leigh A
LA
Steensma
David P
DP
Camoriano
John K
JK
Elliott
Michelle A
MA
Pardanani
Animesh
A
Ansell
Stephen M
SM
Call
Timothy G
TG
Colon-Otero
Gerardo
G
Schroeder
Georgene
G
Hanson
Curtis A
CA
Dewald
Gordon W
GW
Kaufmann
Scott H
SH
D000328:Adult; D000368:Aged; D001549:Benzamides; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000187:drug effects; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases