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New Combination Therapies for Follicular Lymphoma

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Published on December 28, 2020

Experts Share Exciting News in Follicular Lymphoma Treatment

Promising news for follicular lymphoma patients was presented at this year's American Society of Hematology (ASH) conference, including new combination therapies and advancements in CAR T-Cell therapy and bispecific antibody treatment.

Dr. Stephen Ansell, MD, PhD, of the Mayo Clinic explains balancing the benefits and risks of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies. Also reported at ASH 2020, Dr. Ansell introduces the VIPER regimen: the combination of venetoclax, ibrutinib, obinutuzumab, and lenalidomide. The follicular lymphoma treatment space is changing fast. Watch to learn more!


Transcript | New Combination Therapies for Follicular Lymphoma

Dr. Ansell: Hi, my name is Steve Ansell. I am a Professor of Medicine at Mayo Clinic in Rochester, Minnesota. I chair the Lymphoma Group at the Mayo Clinic.

And really exciting data in follicular lymphoma was recently presented at the American Society of Hematology, the ASH meeting this year in 2020. And there are actually multiple different areas of research in follicular lymphoma, all of which have been very promising. But what I'd like to do is highlight maybe three. 

CAR T-Cell Therapy for Follicular Lymphoma

The first is utilizing the immune system as a way to really target the cancer. And this has been a strategy that has been very promising in aggressive lymphomas, like large cell lymphoma, but now the information is transitioning toward lower grade lymphomas like follicular lymphoma. And presented at this ASH meeting was a result of a CAR T-cell strategy, and reminding people that CAR stands for chimeric antigen receptor, which means that the T-cells are genetically engineered to have a specific little docking site on them that will stick them to the tumor cell and allow the T-cells to become activated and kill that cell.

That's proven to be very effective in large cell lymphoma. The question was, would it be as effective in low grade lymphomas like follicular lymphoma? And the answer was a resounding yes. Data that was presented at this ASH meeting showed that the response rates are very high. Now with follow up going out to about a year, we're seeing excellent durability of those responses. So this is a very effective therapy that could be very promising for follicular lymphoma patients.

Now, one has to stress that the follicular lymphoma patients treated in the study were many times high risk patients, because this does have toxicity, and obviously in follicular lymphoma where there are many effective therapies, balancing the benefit versus the risk is a key part of deciding when CAR T-cell therapy is best. But I think the promise is that this is an excellent treatment with a very good response rate, and the responses appear very durable.

Can Bispecific Antibodies Be Used to Treat Follicular Lymphoma?

And similarly, another way to actually get the immune system to be targeting the tumor is the use of a strategy called a bispecific antibody, where T-cells are captured with an antibody and stuck to the B-cell with an antibody strategy, and so the two are brought very close together. The cell then becomes activated and targets the tumor. And again, this strategy has been proven to be quite effective in patients with follicular lymphoma. So what I hope you're hearing is that immunotherapy approaches, either with CAR T-cell therapy or bispecific antibodies, both of these have proven very effective in follicular lymphoma patients.

A second, very promising piece of information from the ASH meeting are additional, what we call small molecule inhibitors. Follicular lymphoma cells and other lymphoma cells really rely on messages that they get from the environment to keep them activated and growing. And if you can switch off those messages, you can really shut the cell down and cause it to die off. And data shared about what is called an IRAK-4 inhibitor, IRAK is part of this messaging system, and if you cut the wire as it were, and switch off this messaging system, that will actually then cause the cell to die off and data that was presented show that this is again a very effective treatment for patients with follicular lymphoma. So, these small molecule pill-type therapies are also proving very promising in follicular lymphoma.

Combination Therapies for Follicular Lymphoma Treatment

And the final way is to maybe combine multiple agents that we know to be effective. And many people will know the drugs like venetoclax (Venclexta), which targets a protein called BCL2, which has to do with keeping cells alive rather than causing them to die off. Ibrutinib (Imbruvica), which is a BTK inhibitor, which is again one of these outside messaging systems. And if you inhibit that, that will shut the cell down. There is an antibody that sticks on the outside called obinutuzumab (Gazyva), which is a CD20 antibody, similar to rituximab (Rituxan), and that can again, cause the cell to die off. And if you combine all of this together and add a further immune modulating drug called lenalidomide (Revlimid), which is a way in which the environment in which the cells grow can be changed, you might come up with an interesting and effective combination for patients with lymphoma. So this combination has the name of ViPOR, and it's all of those drugs together. Many of them, a pill type of treatment. And again, with this combination, highly successful and effective therapy.

All of this to say that I think the follicular lymphoma treatment space is changing fast. We're seeing multiple new drugs and multiple new strategies. Some of them immunological, some of them a small molecule inhibition, all of it looking very promising. Our goal and key is going to be for us to work out what's the best way to combine them? As I say, this ViPOR regimen looks promising, but it's a little complicated and lots of agents together. We might be able to get equally effective therapy with fewer and less side effects. So all of that really encourages patients to participate in clinical trials because that's the way we get the answers, like we just heard at this ASH meeting.

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