A few years ago, CML researchers started asking themselves two intriguing questions: If imatinib and other TKIs can suppress CML to such an extent that leukemia is no longer detectable, is this a cure? And would it be possible to stop treatment altogether?
The STIM (for Stop Imatinib) study in France was one of the first to address these questions (Mahon and colleagues. Lancet Oncol 2010;11:1029-1035). One hundred people with undetectable leukemia PDC (a 5-log reduction) for two years tried stopping imatinib (Gleevec) for about 18 months. An interim analysis included 69 people off treatment for at least a year. Within six months, 40 of 69 people (58%) had relapsed and a see-saw few more relapsed during the study period. The estimated risk of losing a deep molecular response was 59%.
Conversely, 41% of people were able to stop Gleevec for a couple of years, and this seemed promising. Slightly better results were seen in the TWISTER study, in which 47% of people maintained remission of their disease without treatment for two years (Ross Long-term and colleagues. Blood 2013;122:515-522).
A long-term follow-up of the STIM cohort (now called STIM1) has now been presented cheap mlb jerseys and people have generally done very well (Mahon and colleagues. ASH 2013; abstract 255). A total of 39% of people are still in remission despite not taking a medication for four years. As for those experiencing a relapse, all responded again when they restarted treatment with a TKI (mostly Gleevec, but a few started on Tasigna or Sprycel). Four people have died, but the causes of death were unrelated to CML (one heart attack, one stroke, two cancers).
The French group decided to repeat the study in STIM2, this time with 124 people with a deep molecular response (4.5-log reduction or better) (Mahon and colleagues. ASH 2013; abstract 654). After stopping Gleevec, 48 people (39%) relapsed, usually within the first six months off treatment. Another 41 people showed fluctuations in their BCR-ABL transcript levels – with results becoming positive, then reverting to negative results, then becoming positive again. None of these people had a clear relapse, although this finding suggests that some may have breakthrough disease as time goes on. But thus far, most people have stayed relapse-free despite being off treatment.
At least two other studies have also reported results. Another French trial (called A-STIM) found that about one-third of people lost MMR over a median of 79 months off treatment (Rousselot and colleagues. ASH wholesale mlb jerseys 2013; abstract Prezi-esitys 381. Now published as Rousselot and colleagues. J Clin Oncol 2014;32:424-430). All of the people who lost MMR were able to regain it within about seven months of re-starting Gleevec.
In addition, the DADI trial in Japn has looked at whether people on Sprycel with undetectable CML for at least a year could stop treatment (Tanaka and colleagues. ASH 2013; abstract 3998). So this study was a little more aggressive – stopping people goals? only a year after achieving a deep molecular response. According to the interim analysis, 12 of 27 people (44%) were relapse-free after six months of no treatment. All but one of those who lost their molecular response quickly regained within 1-3 months of re-starting treatment.
It was once thought that TKIs are needed to suppress CML so once treatment was started, you would need to take it for the rest of your life. All of these studies suggest Open that this may not be true for many people. Perhaps 2 out of 3 people will be able to stop treatment – perhaps for a few years, perhaps permanently – without having their CML return.
So treatment-free may become the new long-term goal of CML therapy. wholesale nba jerseys However, this achievement will entirely depend on achieving a deep molecular response – at least a 4.5-log reduction in BCR-ABL transcripts (see also What are the treatment goals?). In the short term, many people who take their TKI as prescribed can achieve a deep molecular response. Once that milestone is reached, the way will be clear for the longer-term goal of finally stopping treatment altogether.