'Exciting Advancements' Coming in The Treatment of Lymphomas
The development of bispecific antibodies and antibody drug conjugates could be exciting advancements for patients with lymphomas, including mantle cell lymphoma, according to Dr. Ian Flinn.
BY Dr. Ian Flinn
PUBLISHED May 26, 2020
In a recent interview with CURE®, Dr. Ian Flinn, director of lymphoma research at Sarah Cannon Research Institute, discussed why all patients with lymphomas, including mantle cell lymphoma, should participate in clinical trials, as well as what other treatments, aside from CAR T-cell therapy, are being developed.
“There's this perception that clinical trials are really only for patients for whom other things aren't working anymore,” Flinn said. “… We really need to get away, hopefully, from this notion that it's only for people for whom other therapies aren't working.”
Flinn then went on to explain how new approaches which use the immune system and targeted chemotherapy to fight cancer, including the use of bispecific antibodies and antibody drug conjugates, could offer patients options they may not have had before.
CURE: A lot of these novel drugs are in clinical trials right now. Who should consider a clinical trial? And why is this something that patients might want to talk to their doctors about?
Flinn: I really think that anybody - patients with mantle cell lymphoma or other any other disease that requires treatment - should really think about entering into a clinical trial and talk to their doctor about it.
There's this perception that clinical trials are really only for patients for whom other things aren't working anymore. And I don't think that's true at all. I mean, some of our therapies are available through clinical trials in the frontline setting. And sometimes that's where the most major impact is, when new therapies are in the frontline setting rather than in relapsed or refractory (setting), where the patient has had multiple prior therapies.
So, we really need to get away, hopefully, from this notion that it's only for people for whom other therapies aren't working. And I would encourage our patients and family members to talk about clinical trials with their physicians, with their doctors, at the beginning of any therapy.
Is there anything that I didn't ask that we should have talked about regarding just the general treatment landscape? What's coming along in the pipeline for this disease?
I think there are a lot number of different therapies that are coming along for patients with a variety of lymphomas, including mantle cell lymphoma. We talked a little bit about CAR T-cells, we talked about Bruton’s tyrosine kinase inhibitors, but there are other ways of harnessing the immune system and there are other ways of using targeted chemotherapy.
One exciting advancement is the development of bispecific antibodies. An antibody is targeted therapy. I explain it to most of my patients by saying if I gave you a flu shot, you would develop an antibody that prevents you from getting the flu in the laboratory. We can make antibodies to target anything we want. Rituximab is an antibody that targets an antigen on the surface of lymphoma cells called CD20. It was the first antibody approved for cancer therapy, and now, many different antibodies have been approved. But this is what's called a naked antibody, meaning it's just using the direct binding and its interaction with the immune system to kill cancer cells.
Well, now what's being developed are a couple other approaches. One is a bispecific antibody (which) does two things. It attaches to the lymphoma and another arm of the antibody engages the immune system, our white blood cells, and it brings these white blood cells, these lymphocytes, into close contact with lymphoma to allow what's called an immunological synapse to occur. Basically, that close connection allows the white blood cell to kill the cancer cell. So that's a very exciting therapy, and we're hoping that it’s sort of an off-the-shelf, easy therapy to give for patients compared to some of the difficulties in developing CAR T-cells and these individualized treatment options.
Another approach is through antibody drug conjugates. The antibody drug conjugates that are being developed, one is already approved for other forms of lymphoma, but there are other antibody drug conjugates that are in the pipeline. An antibody drug conjugate is basically an antibody that targets the lymphoma, but at the end of the antibody is a piece of chemotherapy that's been attached to it.
So, by doing this, we're targeting the chemotherapy directly to the malignant cell, to the lymphoma. And the notion is that we can get a very targeted chemotherapy with higher doses to the lymphoma and spare the rest of the body from some of the side effects that you normally associate with chemotherapy. So that's another exciting approach that that's being developed as well.