How often are patients refractory to induction therapy and if this happens, what’s next for these patients?

How often are patients refractory to induction therapy and if this happens, what's next for these patients? So the question is how often a patient is refractory to induction therapy and if that happens what the next plan of treatment is going to be. The refractoriness in general on the average say about 30% of the patients with newly diagnosed AML are refractory to frontline treatment. Whether it's an intensive chemotherapy or whether it's lower intensity regimens which say hypometallic agents and venetoclax. Ballpark number is about 30% or so. Now it again depends on the risk profile of the disease. This profile as we talked before is mostly based on the chromosomal abnormalities and the mutation on profile. If you have what we call the favorable risk group, there the chance of refractory disease is pretty low. 90 plus percent of the patients actually respond to the frontline treatment. In the intermediate group now that percentage increases to possibly about 20 to 30%. Now when you get to the adverse risk group that can go from 40 to 50%. So a lot of the refractoriness can be defined or to an extent somewhat predicted by the pretreatment features also. So in the ballpark number is about 30% but again it is more defined by what risk group the patient fits into. If a person is refractory to the frontline treatment, what are our options? I think still at this point the best option is a stem cell transplant. Even if the patient is refractory to treatment, if we can give fairly intensive chemotherapy to basically wipe out the marrow and proceed with a stem cell transplant that possibly provides the best potential option. Now because of either non-availability of a donor or age or other comorbidities that does not allow the person to proceed to a stem cell transplant, the next option would be to look at targetable mutations. Say if somebody has an FL3 mutation or an IDH mutation where there are potential drugs that can target those mutations. So that would be the next look. Now the chances of one of those being present is going to be lower because most likely you would have detected that at the baseline itself. But it's still, we do see surprises that in about 10-15% of the patients we may see mutations emerge which we could not detect at baseline but when the disease is refractory we detect that and those patients can go into that targeted treatment pathway. But at this point I still believe if you cannot go for a stem cell transplant the best option is still a clinical trial. It could be a combination of drugs that are already in the market or drugs that are being developed in combination with drugs that are already available in the market. So the availability of clinical trial and making a clinical trial available to patients across the country even in people who live in remote areas I think is an extremely important thing that we all investigators need to look at how to deliver that there and possibly through development of more networks. In this context for primary refractory disease there is nothing that is approved. So you have to be innovative either have an innovative combination of some of the established agents or better take part in a clinical trial.