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New and Emerging Therapies for Follicular Lymphoma

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Published on May 7, 2021

What Are the New Therapies for Follicular Lymphoma?

"We are in the middle of a historic time in the development of new treatments for indolent non-Hodgkin's lymphoma like follicular lymphoma," says Dr. Peter Martin, MD, Chief of the Lymphoma Program at Weill Cornell Medicine. In this segment, Dr. Martin offers an overview of the momentum of drug development for follicular lymphoma over the past few years, including the two that are already approved in 2021: umbralisib (Ukoniq) and the CAR T-cell therapy axicabtagene ciloleucel (Yescarta). Watch to learn where we are headed next for the treatment of follicular lymphoma.

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Transcript | New and Emerging Therapies for Follicular Lymphoma

What Are the Emerging Therapies for the Treatment of Follicular Lymphoma?

Dr. Martin: We are in the middle of a historic time in the development of new treatments for indolent non-Hodgkin's lymphoma like follicular lymphoma. We've seen over the past five years, a number of new drugs approved. Really over the... Already in 2021, two new treatments approved in follicular lymphoma already. These were, more specifically, umbralisib (Ukoniq) and the CAR T-cell axicabtagene ciloleucel (Yescarta). So, these are added to multiple other intravenous chemotherapies, monoclonal antibodies and other oral targeted drugs including lenalidomide (Revlimid) and the PI3-kinase inhibitors, idelalisib (Zydelig), copanlisib (Aliqopa) and duvelisib (Copiktra) and I mentioned umbralisib. In fact, just last week at the AACR meeting, we saw the first completion of a phase three trial in indolent non-Hodgkin lymphoma, looking at the combination of copanlisib plus rituximab (Rituxan) versus rituximab alone, and that was a positive trial. So, lots of excitement with new treatments available in follicular lymphoma.

We're also going to see, I think in the near future, hopefully, bi-specific antibodies approved in follicular lymphoma. I forgot to mention tazemetostat (Tazverik). That's how many there are, it's hard to keep track of them all. Tazemetostat is an oral Pch2 inhibitor, so definitely exciting times in follicular lymphoma. One of the interesting questions is, with new treatments available that are arguably more effective and better tolerated than what we've had historically, which was primarily chemotherapy, is there a scenario where our general approach to follicular lymphoma could change? I'm sure many people know this, but in follicular lymphoma, our goal historically has been to manage the lymphoma with the intention of minimizing lymphoma-related symptoms, and also minimizing treatment-related side effects. In that vein, there has never really been any strong evidence to suggest that early treatment of follicular lymphoma improves long-term outcomes. So, most people with follicular lymphoma are going to live a normal lifespan, similar to age-matched controls without lymphoma.

And applying chemotherapy early on in somebody who doesn't have symptoms, without a lot of tumor bulk, for example, simply adds to the side effects that this person is going to experience without extending their long-term survival.

What Should Patients Know About Deferring Treatment?

And so historically we have typically deferred treatment in people who don't necessarily need it at the time of diagnosis. That's usually about somewhere around a quarter of all patients may not have any symptoms and may be reasonable candidates to be observed, maybe larger than that, but in observational series, it's always been about a quarter of patients. As we have new treatments available that have the potential to be more effective and better tolerated, could there be a scenario where we start to use those treatments earlier? I think it's a reasonable question, but we don't really have those data yet. We're going to have to start to use these newer treatments earlier and earlier, as earlier and earlier lines of therapies, potentially combining them with other kinds of targeted therapies or immunotherapies. And then at some point we're going to have to embark on those trials, looking at earlier therapy versus the standard, which is watch and wait.

One of the challenges is, because outcomes in follicular lymphoma take so long, people live for decades, quite literally, it can take a long time to get the answers for those trials. And indeed, if one were to wait 20 years for one of those trials to be completed, undoubtedly a number of other therapies would have been approved in that period of time, potentially making that trial irrelevant. So, I think it's a great question, it's one that we often ask ourselves. I think many of us will admit that if we're not trying to cure follicular lymphoma, then we're not doing our job as researchers, but there are certainly a number of challenges in designing a trial that could prove that we should be treating people earlier rather than watching them. So, for the time being, I think a watch and wait strategy is appropriate for many patients and they can do so confidently knowing that they're going to most likely live a normal lifespan and that in that lifespan, we're likely to see multiple kinds of new treatment modalities approved, including treatments with a curative potential.

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