Most people with CML start treatment with Gleevec, the first TKI that became available fifteen years ago. Another option, however, is to start with one of the more potent second-generation TKIs (e.g. Sprycel, Tasigna), which can achieve a more rapid control of the CML disease process.
Several studies have now shown that people do better over the short and long term when one of these second-generation medications is used instead of Gleevec. The most recent analysis looked at people in the DASISION trial, in which people started treatment either with Gleevec or Sprycel (Shah and colleagues. ASCO 2016; abstract 7055). The benchmark of treatment success was a 1-log reduction within the first three months – an early response that has been shown to result in better long-term outcomes (Baccarani and colleagues. Ann Hematol 2015;94 Suppl 2:S141-47).
Overall, 84% of people in the DASISION study who took Sprycel achieved this level of disease suppression compared to 64% of those taking Gleevec. For the present analysis, the investigators looked at people grouped according to their risk of disease progression. In the low-risk group, 91% in the Sprycel group versus 73% in the Gleevec group had an early response. The advantage was most apparent in the highest-risk group: 83% of people treated with Sprycel had an early response compared to only 44% of those taking Gleevec.
Similar results were seen in a U.S. study of Tasigna (Cortes and colleagues. J Clin Oncol 2010;28:392-397). A total of 49 of 51 people (96%) starting treatment with Tasigna had an early response (a 2-log reduction in the first three months). Over the longer term, more potent second-generation medications have been shown to result in very good outcomes. In the GIMEMA phase II study, over a 6-year period the proportion of people with a major molecular response (i.e. a 3-log reduction) was 98% (Gugliotta and colleagues. Haematologica 2015;100:1146-1150). Of particular importance, 1 in 3 people achieved a stable, deep molecular response – so they might be eligible to stop treatment altogether.