How is risk stratification used in making treatment decisions? What is risk-adaptive therapy?

How is risk stratification used in making treatment decisions?

What is risk adaptive therapy?

Risk can be used to determine therapy piece only in a very limited fashion. Currently, there are clinical trials underway to try and understand if patients with higher risk should be managed differently. But there are a few things that need to be considered.

One, there have been trials in Europe that demonstrate that patients who have high risk disease may benefit from two consecutive transplants instead of one. Now, whether that's applicable globally is difficult because in European Union, access to the same medications that we have in the United States, it isn't the same. And so whether the availability of modern drugs obviates the need for two transplants, unclear. But certainly in the EU, high risk is considered for two transplants.

Some clinicians change the way in which they do maintenance therapy in high risk versus standard risk outside of a clinical trial. Some centers will use two or three medications for maintenance therapy instead of one medication for maintenance therapy for a high risk, because of their concern that they have an increased risk of early recurrence of the disease and in some instances, risk may determine how long you're going to give maintenance therapy, whether it has to be abbreviated or whether it will be more indefinitely defined duration of therapy.

But a lot of the research ongoing now is trying to figure out whether high risk patients should be treated with four medications. That induction at diagnosis versus three medications at diagnosis. But these are still the subject of research, and it's hard to definitively say whether risk should be used in day to day clinical decision making.

The final is that there can be targeted therapies for one of the bad genetic variables the 11;14 translocation, which is considered a high risk feature. Those patients may be uniquely sensitive to the oral medication venetoclax. And for patients who have their genetic abnormality, some physicians will consider the use of their drug venetoclax as part of this management of their disease.

So this is a very controversial area right now and one where there's a lot of research going on. But there are certain abnormalities within the bone marrow chromosomes that lead to what we call higher risk disease, a higher likelihood that the disease either won't respond to standard treatments or will respond, but only for a short duration of time. And so we are sometimes able to use this risk stratification information to tailor the treatment to the patient.

In some cases, this means we might use the different initial regimens, more aggressive therapy, or in some cases we may recommend a different type of maintenance therapy, perhaps two different drugs used together rather than one drug. If the patient has high risk disease. In addition, there are a number of clinical trials now going on that are specifically focusing on patients who have some of the higher risk cytogenetics or higher risk laboratory abnormalities to try to see if we can change our interventions, perhaps to get better outcomes in this group of patients.

So that's how we're using the information now.