Christine Kujak1, Jill M Kolesar2. 1. University of Wisconsin-Madison School of Pharmacy, Madison, WI. 2. University of Wisconsin-Madison School of Pharmacy and University of Wisconsin Carbone Comprehensive Cancer Center, Madison, WI. jill.kolesar@wisc.edu.
Abstract
PURPOSE: Treatment options for chronic-phase chronic myelogenous leukemia (CML) based on medication-resistant mutations in BCR-ABL are reviewed. SUMMARY: Imatinib, nilotinib, and dasatinib are first-line therapies for chronic-phase CML. Nilotinib or dasatinib can be used as first- or second-line treatment, with nilotinib preferred in patients with BCR-ABL F317 and V229 mutations and dasatinib in patients with Y253H, E255, and F359 mutations. All three medications are associated with neutropenia, thrombocytopenia, and anemia; the reported rates varied but ranged from 38% to 90% in Phase III studies. Although less data are available for bosutinib, the drug can be used as second-line therapy and is effective against F317L, Y253H, and F359 mutations. Mutations at position T315I are generally resistant to all of these tyrosine kinase inhibitors (TKIs) but may respond to ponatinib or omacetaxine. The choice of third-line therapy can be driven by mutational analysis or patient-specific characteristics. While ponatinib and omacetaxine have activity in patients with T351I mutations, they have not been directly compared. Differences in patient characteristics and adverse-effect profiles may also aid in the selection of appropriate therapy. CONCLUSION: Several TKIs are effective in the treatment of chronic-phase CML. Imatinib, nilotinib, or dasatinib may be used as first-line therapy, while second- and third-line treatments are determined based on previous failed therapy as well as BCR-ABL mutation status.
PURPOSE: Treatment options for chronic-phase chronic myelogenous leukemia (CML) based on medication-resistant mutations in BCR-ABL are reviewed. SUMMARY: Imatinib, nilotinib, and dasatinib are first-line therapies for chronic-phase CML. Nilotinib or dasatinib can be used as first- or second-line treatment, with nilotinib preferred in patients with BCR-ABL F317 and V229 mutations and dasatinib in patients with Y253H, E255, and F359 mutations. All three medications are associated with neutropenia, thrombocytopenia, and anemia; the reported rates varied but ranged from 38% to 90% in Phase III studies. Although less data are available for bosutinib, the drug can be used as second-line therapy and is effective against F317L, Y253H, and F359 mutations. Mutations at position T315I are generally resistant to all of these tyrosine kinase inhibitors (TKIs) but may respond to ponatinib or omacetaxine. The choice of third-line therapy can be driven by mutational analysis or patient-specific characteristics. While ponatinib and omacetaxine have activity in patients with T351I mutations, they have not been directly compared. Differences in patient characteristics and adverse-effect profiles may also aid in the selection of appropriate therapy. CONCLUSION: Several TKIs are effective in the treatment of chronic-phase CML. Imatinib, nilotinib, or dasatinib may be used as first-line therapy, while second- and third-line treatments are determined based on previous failed therapy as well as BCR-ABL mutation status.
Authors: Angela Proctor; Imola G Zigoneanu; Qunzhao Wang; Christopher E Sims; David S Lawrence; Nancy L Allbritton Journal: Analyst Date: 2016-10-17 Impact factor: 4.616