What is the role of targeted therapy in ALL treatment and which patients benefit the most?
We're very fortunate, in fact, to have a number of targeted agents in ALL. That it really has changed the landscape of how we treat patients. Almost all patients at this point with a B cell ALL are receiving some form of targeted agent within the course of their therapy.
I'll give two examples. One of them is blinatumomab. Both these examples that I'm going to give you are immune therapies. So blinatumomab is in the category of bispecific T-cell engager. So it's an antibody or a fragment of an antibody that binds to both the lymphoblastic B-cell leukemia cells, as well as the patient's own T cells. And T cells are responsible in part for killing off cancer cells. But what this drug does is actually introduces the cancer cells to your own immune system so that your immune system can go and kill off that leukemia cell. It's a really innovative drug, and it's the first in its class. There are many of these types of drugs that are being used in many different cancers right now. But we're very lucky that we have this. This is overall a very tolerable drug and has some early side effects usually, but most patients tolerate it. And there are many new versions of this drug that are being investigated to be delivered in an easier fashion than blinatumomab is given.
The other one that a lot of patients might hear about is something called inotuzumab. So again, similar to blinatumomab, it's immune drug. It's an antibody that targets protein that's expressed on the surface of the cancer cells, and it carries with it this little molecule of toxic chemotherapy. But because it binds to the cancer cell and then is engulfed by the cancer cell and delivers that chemotherapy directly into the inside the cell, it's a much more targeted approach than giving chemotherapy infusion through the veins where all the cells are exposed to the drug. Certainly both of these drugs have toxicities, but the toxicity profile is very, very different from the kinds of side effects that people hear about with kind of older chemotherapies.
Around a quarter of patients with acute lymphoblastic leukemia have a type known as Philadelphia chromosome positive acute lymphoblastic or BCR-ABL-positive acute lymphoblastic leukemia. And this is a subtype where there is an abnormal gene fusion of the genes BCR-ABL in chromosomes nine and 22 that generates an abnormal cancer protein that essentially is active all the time and causes the cells to divide more rapidly. And there's a whole class of targeted therapies called ABL or ABL kinase inhibitors. They can shut down that process that's driving the cells forward. And so patients with Philadelphia chromosome positive ALL almost universally benefit from incorporation of a targeted therapy into their regimen.
A number of these drugs are also used in chronic myeloid leukemia. And they can include agents such as imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and others.
Now, there are some patients that have other gene fusions that result in abnormally active cancer proteins that may be targetable with these therapies as well. For example, some patients that has Philadelphia chromosome like acute lymphoblastic leukemia may benefit from incorporation of targeted therapies. That's part of the reason why we screen all of our patients at diagnosis for abnormal gene fusions that could give rise to these abnormally active proteins.
There are a number of other targeted therapies that are under investigation in patients with acute lymphoblastic leukemia, including venetoclax, which may be a helpful addition, particularly in patients who have progressed on other treatment regimens, or for patients who are older and may not as easily be able to tolerate components of intensive therapy.