Treatment-free remission – the possibility that some people may be able to stop taking their medication – is the hottest topic in CML research. The idea is that if you can achieve a deep enough response to a medication, the leukemia will be so suppressed that it won’t be able to pose any further problems. The usual benchmark for deep response is a 4.5-log reduction on the PCR results (MR4.5), which means that the amount of cancer proteins being produced has been reduced to less than 1/10,000th of a standard reference.
Studies looking at treatment-free remission have generally involved a small number of people. But now the largest trial to date has found that most people achieving a 4.5-log reduction can safely remain off treatment for an extended period, according to data from at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago and posted online last week.
ENESTop is a phase II study of people treated for at least three years, initially with Gleevec and then switched to Tasigna for at least two years (Hughes and colleagues. ASCO 2016; abstract 7054). People then took Tasigna for another year to consolidate their response.
A total of 127 people stopped treatment after a median of 7 years of taking a medication (including 4-5 years taking Tasigna). Overall, 58% of people were able to maintain a treatment-free remission for a year. The other 42% lost their major molecular response and needed to re-start Tasigna. Almost everyone (98%) who re-started soon regained their major molecular response (a 3-log reduction or better), including 92% who re-attained MR4.5. The median time to re-attain MR4.5 was 13 weeks.
One of the important benefits of being treatment-free was a reduction in adverse effects. During the treatment-free period, there was a low rate of moderate/severe muscle or bone pain (1.6%), and no moderate/severe cardiovascular events or fluid retention (0%).
These results indicate that most people who achieve a deep molecular response can safely stop treatment for at least a year. For those who run into trouble, control of their CML can be re-established within a few months of going back on therapy.
We’ll examine this issue further in our continuing coverage of ASCO 2016.