TY - JOUR
T1 - Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase
AU - Santos, Fabio P.S.
AU - Kantarjian, Hagop
AU - McConkey, David
AU - O'Brien, Susan
AU - Faderl, Stefan
AU - Borthakur, Gautam
AU - Ferrajoli, Alessandra
AU - Wright, John
AU - Cortes, Jorge
PY - 2011/8
Y1 - 2011/8
N2 - Background: Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods: We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinibrefractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 3 weeks. Results: The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities. Conclusion: Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.
AB - Background: Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods: We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinibrefractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 3 weeks. Results: The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities. Conclusion: Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.
KW - Bortezomib
KW - Chronic myelogenous leukemia
KW - Proteasome inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84555204856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84555204856&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2011.06.004
DO - 10.1016/j.clml.2011.06.004
M3 - Article
C2 - 21816374
AN - SCOPUS:84555204856
SN - 2152-2650
VL - 11
SP - 355
EP - 360
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -