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Combination Therapies and Newly Approved Treatments for MCL

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Published on December 30, 2020

Mantle Cell Lymphoma Treatment Options & Clinical Trial Results

Treatment options for mantle cell lymphoma (MCL) are giving hope to patients, with recent news including the long-term success of several combination therapies in clinical trials and newly approved treatments such as CAR T-cell therapy. In this segment, Dr. Peter Martin, MD, of Weill Cornell Medicine shares an overview of the available treatments for MCL patients, including the combination of lenalidomide plus rituximab, which is still proving effective in patients that have been on the treatment for seven years or more, the combination of ibrutinib and rituximab, which still shows promise three years into trials and the ins and out of CAR T-cell therapy. Keep watching to learn more.


Transcript | Combination Therapies and Newly Approved Treatments for MCL

Dr. Martin: Hi, I'm Peter Martin from the lymphoma program at Weill Cornell Medicine in New York. This year at ASH 2020, there were some interesting developments to come in mantle cell lymphoma. I think what we're starting to see is an era of medicine that's emerging that's leaving chemotherapy behind. There were a few trials that had some chemotherapy backbone, but what we're starting to see is more and more exciting data using non-chemotherapy regimens.

How Effective are Combination Therapies in Treating Mantle Cell Lymphoma?

For example, Dr. Sam Yamshon, who's a fellow at Cornell with us presented a seven-year follow-up on a clinical trial run by Dr. Jia Ruan, looking at the combination of lenalidomide (Revlimid) plus rituximab (Rituxan) in people with previously untreated mantle cell lymphoma. And we found that with over seven years of follow-up, this regimen is still very effective and appears to be comparable to what you might expect with chemotherapy with a different side effect profile. Out of MD Anderson, we saw the combination of your ibrutinib (Imbruvica) and rituximab in both younger and older patients. That's data that was previously presented. But now with over three years of follow-up, we see that that's still looking quite promising. So, that's exciting.

The other thing we're starting to see is that in people who are receiving BTK inhibitors, like ibrutinib in second-line or third-line setting, that there may be advantages to combining or adding additional drugs to those agents. For example, venetoclax (Venclexta) combined with ibrutinib and rituximab appears to be quite active. Lenalidomide plus rituximab and venetoclax also appear to be quite active. Two separate trials, both looking quite interesting and promising. Ultimately I think, we're going to see emerging relatively rapidly is when BTK inhibitors are used in their currently approved setting, which is in their previously treated population, they're going to be combined with other drugs.

We're also going to be seeing those combinations moving in the frontline setting, essentially displacing chemotherapy. And I don't think it's going to be very long before we start to see that becoming quite an acceptable standard. May still be a few years, but it's coming pretty clearly.

What Should MCL Patients Know About Immunotherapy and CAR T-cell Therapy?

The other thing that I think is coming is an era of immunotherapy. We saw this recently with the approval of brexucabtagene autoleucel (Tecartus), a CAR T-cell for people with mantle cell lymphoma that's previously been treated. And now we're starting to see more mature data coming from that trial, it's called ZUMA-2 trial. We're also seeing other CAR T-cells, lisocabtagene maraleucel (liso-cel) being used in mantle cell lymphoma in the clinical trial setting, also presenting similarly promising data. This is particularly exciting because these are treatments that have the potential to work in mantle cell lymphoma that is historically considered fairly high risk.

We’re also — along a similar line therapy — we're seeing what are called bispecific antibodies and these in a sense, do something similar to CAR T-cells. They essentially bring the immune system into close context with the tumor cells. These obviously don't require a lot of manufacturing. They can be taken right off the shelf and administered immediately and in very small numbers, but with multiple trials altogether, we can see that that treatment approach is also quite promising. It's going to be a little while before we get more data with those agents, but they clearly have activity and they appear to be quite well-tolerated as well.

What Advice Would You Give to A Newly Diagnosed Patient?

I think that pretty much everybody with mantle cell lymphoma deserves a second opinion from somebody or a center that deals with a lot of mantle cell lymphoma. Mantle cell lymphoma is complicated because it's a particularly heterogeneous disease that can present in multiple different ways. And importantly, the biology of mantle cell lymphoma can vary from person to person. Historically we really somewhat naively essentially divided mantle cell lymphoma into two groups based on the person who had it, were they younger or where they're older? But that fails to take into account the real biological heterogeneity of mantle cell lymphoma. And what we're learning is that that biology is a major driver of outcome, number one. But maybe, more importantly, we're learning that that biology may help us to best select certain treatments.

Doesn't mean that everybody needs to be treated in an academic center, but I think a second opinion is certainly warranted. And one of the things that I think is, as terrible as this whole experience with COVID has been, one of the things that it's brought us has been telemedicine. And so we are able to offer people who are normally in situations where they wouldn't necessarily make it to an academic center, we're able to offer them second opinions and help them to understand lymphoma and what their options are. 

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