For patients who have exceptionally long responses to HMA with high risk MDS or AML and not candidate for more aggressive therapy/transplant, do you consider treatment holidays or spacing out doses into longer intervals?

Over time, patients with MDS and/or AML on long-term HMA therapy tend to have lower counts, possibly due to less robust stem cell reserve. In general, we prefer to drop the dose (i.e. from 75mg/m2 to 50 mg/m2 for Azacitidine, from 20 mg/m2 to 10-15 mg/m2 for decitabine) as a first. In some patients, we keep the 4 week schedule but reduce the number of days of therapy (from 7 days to 5 days). As a last result, we may extend the weeks from 4 to 5 weeks. Overall I prefer to reduce dose OR days firs...

In general we continue HMA on a 4-week schedule. We avoid drug holidays between cycles. While it may not be detrimental to do so there is no evidence to indicate this will not increase the relapse rate. There may be older adults, or even younger, for whom an every 4-week schedule is simply too problematic. In these rare instances we consider increasing the intervals to every 5 or 6 weeks. However, we don’t encourage this.

This is a great question. Given the logistical and sometimes financial challenges of long-term administration of hypo-methylating agents, it is not uncommon for patients or families requesting a treatment holiday. There are no randomized clinical trials that have answered this specific question. Spacing out to 5-6 week increments would be preferable given the risks of relapse/resistance.