Highlights from the American Society of Hematology (ASH) annual meeting, San Diego CA, December 3-6, 2016
Perhaps the hottest topic in CML research is whether people can stop taking their medication if they respond well to treatment for an extended period – what has been called “treatment-free remission”, or TFR. The prerequisite for attempting TFR is typically a deep molecular response, usually defined as a 4.5-log reduction (called MR4.5, for molecular response), that is maintained for two or more years. This degree of response means that testing is unable to detect the presence of leukemia (although a small amount undetectable by current tests likely remains). What’s intriguing about this idea is that if leukemia has been undetectable for several years, and you are able to stop your medication without having a relapse, it’s possible that you’ve been cured of your CML without knowing it.
There are two key questions that research still needs to address. The first is: how likely is it that a person who stops a medication will be able to stay off treatment without suffering a relapse? (Note that you should not stop your medication on your own – no matter how good your response. Stopping is not advisable outside of a clinical trial because the study will ensure that you are tested often – if you relapse, you’ll need to go back on treatment immediately.)
The second question is: what happens if I stop treatment and have a relapse? This will be addressed in Part 2.
Several studies at the most recent ASH conference presented results from current TFR trials. The following is a summary of what they found.
Gleevec: The EURO-SKI (for European Stop TKI) study included people on any treatment (Gleevec, Tasigna or Sprycel) who had achieved MR4.0 for at least one year (Mahon and colleagues. ASH 2016; abstract 787). Results were only reported for those stopping Gleevec. Overall, 56% maintained their remission for 1 year, and 52% for 2 years. Among those who lost their response, all were able to re-achieve a deep molecular response after re-starting treatment. No one experienced progression of their CML. How long a person was on Gleevec appeared to be important – results were better if a person had been taking Gleevec for at least 6 years. This differs from studies of Tasigna and Sprycel, in which people are able to try stopping sooner after starting one of these second-generation medications.
Tasigna: The ENESTop trial looked at people who had achieved MR4.5 after switching from Gleevec to Tasigna (Mahon and colleagues. ASH 2016; abstract 1891). Overall, about 58% of people who stopped Tasigna remained in remission after one year off medication. A second study, called ENESTfreedom, looked at people who had only ever taken Tasigna and had achieved MR4.5 (Hochhaus and colleagues. ASH 2016; abstract 3066). Results were similar – about 52% remained in remission after one year. In both studies, people were more likely to report having muscle pain when they were treatment-free compared to when they were taking Tasigna. However, people generally reported fewer side effects once they were off medication, as you’d expect. Some people were understandably anxious about stopping treatment, but ENESTfreedom found that their anxiety level didn’t get worse once they stopped.
Sprycel: DASFREE is a small study that included people who had switched from Gleevec to Sprycel, or had started treatment with Sprycel (Shah and colleagues. ASH 2016; abstract 1895). People were required to have been taking Sprycel for at least 2 years and were MR4.5. A key difference was that loss of remission was defined as loss of MMR (major molecular response, i.e. MR3.0), rather than loss of a deep molecular response (i.e. MR4.5). According to this definition, 63% of people were able to remain off treatment for 1 year. Among those who lost their response, most had to re-start treatment after 4 months or so. People were more likely to do better if they had been taking Sprycel for about 5 years before they tried stopping it. The most common side effects after stopping Sprycel were aches and pains, high blood pressure, and skin problems.