Resistance to tyrosine kinase inhibitors (TKIs) has many facets. The causes of resistance include low patient compliance, low plasma or intracellular drug concentration, BCR-ABL1 mutations, and clonal chromosome abnormalities in Ph+ cells, but in at least 50% of patients the causes are currently unknown. Primary resistance occurs when a predefined response level is not achieved within a prespecified period of time. Not achieving a complete hematologic response (CHR) within 3 months, not achieving a partial cytogenetic response and/or a BCR-ABL1 transcripts level <= 10% (international standard) within 6 months, and not achieving a complete cytogenetic response (CCyR) and/or a BCR-ABL1 transcripts level <1% within 12 months, define primary resistance. Secondary resistance is defined by a loss of CHR, or CCyR, or major molecular response. Resistance to imatinib calls without exceptions for a second-generation TKI. In case of resistance to two TKIs, an allogeneic stem cell transplantation should be considered
Definition and treatment of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia
BACCARANI, MICHELE;CASTAGNETTI, FAUSTO;GUGLIOTTA, GABRIELE;PALANDRI, FRANCESCA;ROSTI, GIANANTONIO
2014
Abstract
Resistance to tyrosine kinase inhibitors (TKIs) has many facets. The causes of resistance include low patient compliance, low plasma or intracellular drug concentration, BCR-ABL1 mutations, and clonal chromosome abnormalities in Ph+ cells, but in at least 50% of patients the causes are currently unknown. Primary resistance occurs when a predefined response level is not achieved within a prespecified period of time. Not achieving a complete hematologic response (CHR) within 3 months, not achieving a partial cytogenetic response and/or a BCR-ABL1 transcripts level <= 10% (international standard) within 6 months, and not achieving a complete cytogenetic response (CCyR) and/or a BCR-ABL1 transcripts level <1% within 12 months, define primary resistance. Secondary resistance is defined by a loss of CHR, or CCyR, or major molecular response. Resistance to imatinib calls without exceptions for a second-generation TKI. In case of resistance to two TKIs, an allogeneic stem cell transplantation should be consideredI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
