Onkológia 5/2012

Future of treatment of chronic myeloid leukemia (CML)

Imatinib has shown exceptional efficacy in the treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML), but onethird of treated patients do not match the criteria associated with an optimal outcome and could potentially benefit from a more effective treatment strategy. Several trials of modified imatinib- based treatments and second- generation agents are ongoing. In some studies, high- dose imatinib (800 mg per day) or imatinib plus interferon was reported to be able to induce higher response rates compared with standard – dose imatinib, however no improvement in progression- free survival or overall survival has been so far observed. On the bases their capacity to induce faster and deeper responses and to prevent at least part of the early progressions to accelerated phases that still occur during the first two to three years from diagnosis, dasatinib and nilotinib have been recently registered as first –line therapy for CML patients, opening the possibility to use different therapeutic strategies for newly diagnosed CML patients. Apart from the continuous improvement of performance over time on the approved CML therapies (ASH, 2011), exciting news were presented on ponatinib (AP24534) and very early data on DCC-2036. Both drugs have the capabilities of targeting T315I, which may be the „last bastion“ in chronic phase CML. It has been shown recently that advances in molecular methods enable to better understand disease itself, weight benefit to risk ratio of the therapy, individualize therapeutic approach and eventually adjust CML therapy earlier in order to minimize the risk of CML progression to accelerated phase.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, imatinib, dasatinib, nilotinib, ponatinib, bafetinib, DCC-2036.