Highlights from the American Society of Hematology (ASH) annual meeting, San Diego CA, December 3-6, 2016 – In previous articles we’ve discussed the most recent information about treatment-free remission (TFR), in which people with a deep molecular response to treatment are able to stop their medication altogether. (See CML-IQ – Updated results from recent Stop trials, Part 1 and Part 2.) In studies to date, about 50% of people have remained in remission for at least a year. The key to success appears to be a deep molecular response, usually defined as a 4-log reduction or better in BCR-ABL transcripts (i.e. leukemia numbers that are 1/10,000th of what they were), sustained for several years.
But rather than go the full monty, is there any merit in taking a half-step toward the goal of being treatment-free? This question was addressed in the DESTINY (for De-Escalation and Stopping Therapy with Imatinib, Nilotinib or sprYcel) study in the U.K. (Clark and colleagues. ASH 2016; abstract 938).
This study set the bar a little lower. People needed to have been on treatment for at least three years, to have been on the same drug for the entire period (unless they needed to switch because of side effects), and to have had a major molecular response (MMR, i.e. a 3-log reduction) for at least a year. If people met all of these criteria, their usual medication dose was cut in half for a year (i.e. to 200 mg/day of Gleevec, 200 mg twice-daily of Tasigna, or 50 mg/day of Sprycel). If, after a year of reduced dosing, they had maintained their response, they could then stop treatment altogether.
Overall, in the group with a 4-log reduction (MR4) at the start of half-dosing, only 2% experienced a relapse; compared to 18% of those with MMR at the start. Those who relapsed were put back on the full dose, and all of them re-gained MMR within three months. No one progressed to accelerated-phase CML, and there were no serious side effects or CML-related deaths during the observation period.
The results of the second part of the study – stopping treatment altogether – haven’t been reported yet. So it isn’t known if half-dosing is worthwhile. Half-dosing did appear to identify those people who are likely to have a relapse if they stop treatment. But it should be noted that people with MMR (but not MR4) wouldn’t have been included in a Stop trial anyway because their molecular response wasn’t deep enough.
The more important finding of this study is that many people with MMR can do very well on a lower dose for an extended period, which would reduce the burden of side effects and lower the cost of treatment. But this strategy should not be done on your own, because you can quickly run into trouble if you start taking a lower dose without your doctor’s knowledge. Talk to your hematologist if your numbers have been good (at least MMR) for several years, but you’re having difficulties staying with the regimen because of side effects. You and your doctor can then decide if lowering your dose is an option for you.