How do immunotherapies treat ALL?

How do immunotherapies treat ALL?

Immunotherapy broadly refers to a range of therapies that harness the power of the immune system to eradicate residual cancer.

Now, some immunotherapies, such as blinatumumab work is what we call bispecific T-cell engager or bites. I explain blinatumumab to patients is like a two headed molecule where one hand grabs a healthy T-cell and one hand grabs a cancer cell and it puts them together.

This is a therapy that is particularly effective in patients that just have either very low level, minimal residual disease or in patients who actually don't even have detectable disease anymore, but whom we think have a level of disease that's below the resolution and what our current technology is able to determine.

There are other immunotherapies that work in different ways. For example, there's a drug called inotuzumab, it bines to a different marker on the surface of the leukemia cell called CD22, and is then brought inside the cell almost like a Trojan horse, where the molecule is then broken up and releases a toxin to the cancer cell. Almost like delivery is sort of a smart bomb of sorts toward the cancer cell.

There are monoclonal antibodies, such as rituximab that bind to something on the surface of the cancer cell that also can be active as a component of therapy, but that we don't really use by themselves. But they can be combined with chemotherapy in patients that have high expression of that marker.

Additionally, CAR-T cell therapy is an exciting form of immunotherapy. there are several CAR-T cell products that are approved currently broadly, we manufacture these products by collecting a patient's own healthy immune cells by a process called leukapheresis which is similar in some ways to donating blood, except instead of donating to someone else, you're basically having your cells collected so that they can be sent to an outside laboratory and engineered for later use in you.

I know that outside lab, we engineer that cell to have an artificial marker or a receptor on its surface that can actually recognize and target the cancer cells specifically, after that cell product is made, it undergoes testing at the outside laboratory to make sure that the product is safe for administration. And then it's frozen until it's ready for use. And then it can be infused through the IV.

CAR-T cells are a form of living drug, in the sense that the drug that is infused into the patient can actually expand and grow. Whereas if we're giving chemotherapy, for example, the dose that's in the bag is the dose the patient receives. And after the CAR-T cell therapy is administered to the patient, those cells can divide and can home to sites of the leukemia in that particular patient.

Patients who undergo CAR-T cell therapy are at risk for a number of side effects, including inflammatory responses that are related to just the activation and division of these, CAR-T cells, as well as a spectrum of largely reversible neurologic side effects.

But broadly, this is using essentially someone's own cells to be able to target residual cancer by going after a marker that's on the surface of the leukemia.

There are a number of CAR-T cell products that are under investigation, both for B-cell leukemia, B-cell ALL, where we currently have the three approved CAR-T cell products, as well as for T-cell acute lymphoblastic leukemia, where we currently don't have any CAR-T cell products that are approved. Although there are a number in the pipeline under investigation.

As I was saying before about blinatumumab and inotuzumab, and there are other immunotherapies that I haven't mentioned, these are being integrated. So they were initially, approved in the relapsed setting. So for people who had received initial chemotherapy for their disease and then unfortunately had a relapse, and we saw that they worked in that setting.

And now there are many studies showing that these are efficacious in the frontline for people who are newly diagnosed, either at the outset of their diagnosis or in that second consolidation phase of their disease.

And one example of that, with blinatumumab, is the fact that this drug has very recently been shown to be to improve survival, in pediatric patients with certain risk features in their disease.

And so that in combination with some older adult data showing that there is also a survival benefit when we integrate that even in people who have very, very good responses to their first induction chemotherapy.

All of this together is demonstrating that these patients really benefit from the integration of this, this therapy, we know that it deepens remission. Appears to improve overall survival.

And in the patients who I treat, who range from, you know, anywhere from 18 years old up to their 90s, it's been particularly beneficial because people, as they get older, really don't tolerate the traditional cytotoxic chemotherapy, this kind of chemo bomb that we throw in people when we need to, but they do seem to tolerate these, antibody therapies very well.

So there are trials looking at combining those two antibody therapies. I mentioned the Inotuzumab and the blinatumumab and only using those and no chemotherapy through the veins for older adults.

And we'll see what the duration of the remissions we can get with that are. But I do think that it's really helping patients from the very young to the very old.