A great deal of attention has been paid to “treatment-free remission” (TFR), where people who have been stable on treatment for many years are able to stop taking their TKI medication.
Stopping treatment altogether may not be an option for many people. But is it possible to take a lower dose to reduce the burden of side effects?
This issue was recently examined in the INTERIM study (Russo and colleagues. Blood Cancer J 2015;5:e347). People aged 65 years or older with well-controlled CML for at least two years were allowed to try a dosing regimen of one month on/one month off. For the On month they took their usual dose of Gleevec; for the Off month, they took no medication.
Over a six-year period, about 1 in 5 people lost their major molecular response (MMR; a 3-log reduction) but retained a complete cytogenetic response (CCyR, roughly a 2-log reduction). About the same proportion lost CCyR, indicating that they were at risk of a relapse. At the end of the 6-year period, just under 50% of people were continuing with the On/Off dosing schedule.
The key concern, of course, is whether those people who lost their treatment response (either MMR or CCyR) were able to regain it. The study found that they could. In the group that lost MMR, all recovered their MMR (including two that achieved a deep molecular response) after restarting Gleevec (one started Tasigna). For those who lost CCyR, all reattained CCyR, including two who went on to achieve MMR. Nine people died during the study from various causes (other cancers, heart disease, lung disease), but none died because of their CML. No one progressed to accelerated-phase or blast-crisis CML.
The main benefit, as you might expect, was a substantial reduction in medication-related side effects – a 50% reduction, according to the study participants.
These results show that some people who have responded well to TKI therapy may be able to take monthly breaks from their medication regimen and suffer no long-term consequences. However, it’s important to keep in mind that “drug holidays” were attempted only after the person had achieved a good treatment response (CCyR or MMR). Interrupting therapy before an adequate degree of leukemia suppression has occurred can invite disaster – if leukemia is only partially controlled, interrupting treatment may allow the leukemia to proliferate and mutate, and you may not be able to regain control.
It’s also important to note that the study involved older people. Younger people with CML may be playing with fire if they try starting and stopping their medication. This probably isn’t a good strategy over the longer term. The study also demonstrates that ongoing treatment is needed to suppress CML: leukemia cells began to proliferate within two years in most people taking a lower dose.
Interrupting treatment isn’t something that should be attempted on one’s own. The subjects in this study had access to frequent blood monitoring, so treatment could be re-started quickly if they ran into trouble. However, for people experiencing intolerable side effects, periodic breaks may be feasible – if your doctor agrees to the plan and closely monitors your blood results.