In recent years, the goal of treating CML has fundamentally shifted from controlling the disease process with a TKI medication (e.g. Gleevec, Tasigna, Sprycel, Bosulif) to something more ambitious: a suppression of CML that is so profound that treatment will no longer be needed. Preliminary studies found that stopping treatment was feasible in people with a deep molecular response that was sustained for one or more years. That finding led to larger studies using various treatment regimens.
The largest study to date, called ENESTop, reported its results at this year’s meeting of the American Society of Clinical Oncology (ASCO). The study involved people on Gleevec who switched to Tasigna for a few years, then stopped treatment. Overall, about 58% remained in treatment-free remission (TFR) – no worsening of their CML – for at least a year (Hughes and colleagues. ASCO 2016; abstract 7054). See Stopping treatment – findings of the largest study to date, CML-IQ, May 26, 2016.
People in the ENESTop trial had been taking a medication for an average of seven years before they stopped treatment. But was it possible to stop treatment earlier?
This was the question explored in a second study called ENESTFreedom (Hochhaus and colleagues. ASCO 2016; abstract 7001). All of the people in this study had started treatment with Tasigna rather than Gleevec or another TKI. Another important difference was that people were on Tasigna for only 3-4 years. Those who achieved a deep molecular response (defined as a 4-log reduction in disease activity, and a 4.5-log reduction at their last assessment) were eligible to stop treatment right away.
Overall, 190 people stopped Tasigna and entered the TFR phase of the study. After one year, 52% remained in remission and didn’t need to re-start their medication. Among those who lost their deep response off treatment, all were able to re-achieve a major molecular response (a 3-log reduction) within two months of starting treatment again, and almost 90% regained their deep response (4.5-log reduction) within four months.
Prior studies have shown that people who start treatment with one of the second-generation TKIs (Tasigna, Sprycel, Bosulif) can achieve a deep molecular response earlier than if they start with Gleevec (Hughes and colleagues. Haematology 2015;100: abstract 229). The results of the ENESTFreedom study now suggest that this early response can mean stopping treatment earlier – within 3-4 years of starting the regimen. This would reduce the time on treatment by a few years. For people with a deep response, there’s a 50:50 chance that they can remain off treatment for at least a year (and avoid many of the medication-related side effects). And for those who unsuccessfully stop their medication, they can simply re-start their medication and be no worse off than they were before.