What are the next steps if I relapse after taking hypomethylating agents with or without venetoclax?

What are the next steps if I relapse after taking hypomethylating agents with or without venetoclax? So the question is that if the disease comes back after responding to hypomethylating agent like decitabine or azacytidine, we told without venetoclax. That's becoming a bigger question in the field because we did not have the kind of successes that we have now with hypomethylating agent and venetoclax. Earlier on in that group of patients we could expect remission rate of at best 20-30%. Now we are talking about average remission rates of 70%. So much larger patient population is going into remission. But the problem is that relapse is still a reality. It may happen in 12 months time, 24 months time, 48 months time, but relapse is still a reality because the median relapsed resurvival is possibly close to about one and a half years to two years depending on your risk profile. So now we are facing that question because these drugs are now approved, people are using it and it's a real question. Unfortunately, it is possibly the most challenging field right now that we have. Now that said, even for quote unquote older patients who are offered hypomethylating agent and venetoclax as a frontline treatment, many of them are physically fit. They may not have a lot of comorbidities. So the question of a more intensive chemotherapy regimen can be still looked at if a person is thought to be physically fit. And the idea in that case would be to see if they can get into a response, may not be the best of remission but at least some sort of a response and then can still be considered for stem cell transplantation. So I would not take intensive chemotherapy or stem cell transplantation completely off the table just because somebody is over the age of 65. Because a lot depends on the patient's fitness level, what comorbidities are there, right? And so those things need to be considered. But beyond that, now it's almost boiling down to a clinical trial really because we're all trying different options. Again if somebody relapses after venetoclax and asocytidine, I would still look for targetable mutations. And it's not uncommon that either a targetable mutation was present at the very beginning or a targetable mutation is emerging now, possibly in about 20% of the patients but it's still 20% where you can actually go with a targeted agent. It could be an IDH inhibitor, it could be an FLT3 inhibitor because they offer the best chance for these patients when they relapse. Even if it's in the 20% of patients, it's worth looking. So the repeat look is important in terms of repeating the mutation profile at relapse because that gives you more treatment options. Now if those targetable options are not there, then the best option is a clinical trial at this point.