Imatinib mesylate therapy for polycythemia vera: final result of a phase II study initiated in 2001.
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by excessive production of red blood cells. Patients with PV are at a risk of thrombosis, bleeding, and transformation to myelofibrosis or acute myeloid leukemia. Therapy for PV is based on the use of phlebotomy, aspirin, and in high-risk patients, cytoreductive agents such as hydroxyurea. Anecdotal evidence suggests that imatinib mesylate, a selective tyrosine kinase inhibitor of ABL1, ARG, PDGFR, and KIT kinases has activity in PV. We conducted an open-label phase II clinical trial of imatinib at the standard dose of 400 mg daily in 24 patients with PV. The median duration of imatinib therapy was 5.1 months (range 0.2-86.4). Overall, 4 (17%) patients responded: one had a complete and three partial hematological response. The median time to response was 17.5 months (range 6-28), and the median duration of response was 17 months (range 9-68). No significant changes in JAK2(V617F) mutation burden were noted during imatinib therapy when compared with pretreatment values (P = 0.46). Therapy with imatinib was generally well tolerated. Our data indicate that imatinib has minimal clinical activity in PV.
Nussenzveig
Roberto H
RH
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.|ARUP Laboratories, Salt Lake City, UT, USA.
Cortes
Jorge
J
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Sever
Matjaz
M
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Quintás-Cardama
Alfonso
A
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Ault
Pat
P
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Manshouri
Taghi
T
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Bueso-Ramos
Carlos
C
Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Prchal
Josef T
JT
Division of Hematology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Kantarjian
Hagop
H
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Verstovsek
Srdan
S
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. sverstov@mdanderson.org.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001549:Benzamides; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D013997:Time Factors
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D016315:Proto-Oncogene Proteins c-abl