Dr. Ian Flinn

®, Dr. Ian Flinn, director of lymphoma research at Sarah Cannon Research Institute, discussed the benefits of Revlimid (lenalidomide) in combination with Rituxan (rituximab) in patients with mantle cell lymphoma.

Another potential option for many patients is the drug lenalidomide in combination with Rituxan, some patients have a more inlet form of mantle cell lymphoma and this is a very reasonable combination for that patient group as well as others. Lenalidomide is a cousin of a drug thalidomide.

Thalidomide was a drug that unfortunately has a terrible side effect, that it caused birth defects. For that reason, it’s a terrible drug but it has great anti-cancer properties where it’s very effective. We now have second and third generation cousins of thalidomide that are very useful. So, lenalidomide in combination with rituximab is an effective therapy for mantle cell lymphoma that voids some of these adverse events that I’m talking about.

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“We now have second and third generation cousins of thalidomide that are very useful. So, lenalidomide in combination with rituximab is an effective therapy for mantle cell lymphoma that voids some of these adverse events that I’m talking about,” said Dr. Ian Flinn. Hear more about this treatment in his interview with CURE®. 
 

Revlimid and Rituxan Combo 'Another Potential Option' For Patients With Mantle Cell Lymphoma

®, Dr. Ian Flinn, director of lymphoma research at Sarah Cannon Research Institute, discussed what treatment for mantle cell lymphoma may look like over the next several years.

“I think we’re in a midst of a real shakeup in our treatment paradigms for patients with mantle cell lymphoma, or at least we will be in the next few years,” Flinn said.

I think we’re in a midst of a real shakeup in our treatment paradigms for patients with mantle cell lymphoma, or at least we will be in the next few years.

One of the most common therapies for patients with mantle cell lymphoma right now is they get induction chemotherapy, sometimes very aggressive chemotherapy, and then follow it with an autologous peripheral blood stem cell transplant. Basically, a way of giving people very high doses of chemotherapy to overcome resistance to lower doses of chemotherapy and keep people in remission for a longer period of time.

I think the hope is that we’ll be able to get rid of that, right, I mean that is a very aggressive therapy, very difficult therapy that many patients, certainly patients above 70 or so, it’s not probably available to them because of the side effects, and sometimes younger patients want to avoid these as well, so some of these combination therapies that I’m talking about. Such as the combinations of BTK inhibitor and venetoclax (Venclexta) or you know therapies like that, are, I think ultimately going to make their way earlier in the course of therapy and hopefully free us from some of these chemotherapy backbones.  

“I think we’re in a midst of a real shakeup in our treatment paradigms for patients with mantle cell lymphoma, or at least we will be in the next few years,” said Dr. Ian Flinn in an interview with CURE®.
 

In the 'Midst of a Real Shakeup': Perspective on Next Few Years of Mantle Cell Lymphoma Treatments

®, 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. 

: 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.

. 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.

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.
 

'Exciting Advancements' Coming in The Treatment of Lymphomas

In recent years, there have been various Food and Drug Administration approvals of Bruton’s tyrosine kinase (BTK) inhibitors for the treatment of patients with mantle cell lymphoma, as well as other cousin diseases including chronic lymphocytic leukemia and other B-cell malignancies.

®, Dr. Ian Flinn, director of lymphoma research at Sarah Cannon Research Institute, discussed the emerging role of targeted therapies, including BTK inhibitors, in the treatment of mantle cell lymphoma.

: Just to look at the larger landscape as well, what's going on with targeted drugs? Is there anything exciting being studied in that regard? 

Flinn: I think that in targeted therapies, there's a lot of action there too. We've known for a while now that the bruton’s tyrosine kinase (BTK) inhibitors, which is an oral medication, or pills that patients take, are highly effective in mantle cell lymphoma. And so, this is a targeted therapy that decreases the survival and stops the growth of mantle cell lymphoma. And it's effective in other cousin diseases like chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia and other B-cell malignancies, but it's also effective in mantle cell lymphoma.

We now have three different BTK inhibitors that have been FDA approved, most recent is zanubrutinib (Brukinsa), but we also have acalabrutinib (Calquence) and ibrutinib (Imbruvica) that have been approved for the treatment of this, and so that's great news. We know that's effective, some of the more recent results show that patients are staying on remissions longer, sometimes a couple years or more. And that's good news, and then (they’re also) more tolerable.

Later generation therapies have less side effects and so people can have a very good, almost normal, quality of life on these medications. I think some of the other news is trying to combine these with other agents. So, these drugs are being added to chemotherapy backbones in trials looking at trying to improve how long someone stays in remission, and response rates. They're being combined with other novel agents such as the drug venetoclax (Venclexta), being used in combination with BTK inhibitors, to deepen the remission and try to get away from a chemotherapy backbone because, you know, everyone knows that chemotherapy has a lot of unintended consequences, side effects. And so the more targeted therapies that we can use, the more likely we can get away from some of these adverse events.

Evidence shows that Bruton’s tyrosine kinase inhibitors, one of many targeted therapies, are highly effective in patients with mantle cell lymphoma.
 

Dr. Ian Flinn

Revlimid and Rituxan Combo 'Another Potential Option' For Patients With Mantle Cell Lymphoma

In the 'Midst of a Real Shakeup': Perspective on Next Few Years of Mantle Cell Lymphoma Treatments

'Exciting Advancements' Coming in The Treatment of Lymphomas

'A Lot of Action' in The Development of Targeted Therapies for Mantle Cell Lymphoma

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