Many people with CML start treatment with a second-generation agent (e.g. Tasigna or Sprycel) instead of Gleevec because they’re more likely to achieve a faster, deeper response with these more potent medications.
But does this short-term advantage translate to benefits over the longer term?
This question was addressed in the ENESTnd study, which looked at people starting out out on Tasigna and which has now presented data for up to five years (Larson and colleagues. ASH 2014; abstract 4541). In that study, 77% of people taking Tasigna achieved a major molecular response (MMR, or 3-log reduction) after five years of treatment (vs. 60% on Gleevec). The proportion of people who progressed to accelerated-phase or blast-crisis CML was also lower in the Tasigna groups (2.1-3.9%) compared to the Gleevec group (7.4%). ENESTnd plans to continue tracking outcomes for 10 years.
In Italy, the GIMEMA Working Party has looked out how well people did after taking Tasigna for at least 6 years (Gugliotta and colleagues. Haematologica 2015; epublished June 25, 2015). Overall, survival at 6 years was 96%. Only 1 of 73 people had disease progression and died of CML. Two other people died of non-CML-related causes (one 75-year-old of dementia and one 90-year-old of heart failure).
After 6 years, 98% had achieved MMR. Responses were typically stable once MMR was achieved, although two people had minor fluctuations. Only one person subsequently lost their molecular response. Moreover, 76% were able to achieve a 4-log reduction (MR4.0) or better.
Thirteen people stopped taking Tasigna during the 6-year period. Four of these had a very good response and were able to enter a Stop trial. Nine people switched to Gleevec or Sprycel. Thirteen people had cardiovascular side effects, and seven of these had to stop treatment. The median age of people with cardiovascular side effects was 69 years; the median time before side effects developed was 46 months. Some people started taking heart medications (e.g. anticoagulants or antiplatelet medications) and were able to continue on Tasigna.
At last report, one-quarter of people starting front-line Tasigna were in stable MR4.0, which means that they are eligible to enter a Stop trial and discontinue treatment.
These results indicate that a high proportion of people starting a second-generation medication can achieve rapid and sustained control of their CML. However, people at risk of a cardiovascular event need to be monitored so they don’t develop heart complications.