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Changing Treatment Landscape for R/R MCL

Panelists: Ian Flinn, MD, Sarah Cannon Research Institute; Javier Munoz, MD, FACP, Banner MD Anderson Cancer Center; Tycel Jovelle Phillips, MD, University of Michigan; Bijal Shah, MD, Moffitt Cancer Center
Published: Wednesday, Feb 12, 2020



Transcript: 

Ian Flinn, MD:
Let’s move beyond first-line therapy for patients with mantle cell lymphoma. Tycel, the landscape is changing. What’s your take on things?

Tycel Jovelle Phillips, MD: Chemotherapy is not really preferred. With more and more of these novel drugs coming out, and especially with the more recent data that Simon Rule has presented on long-term outcomes with ibrutinib in first relapse, my experience has reflected itself in my patient population. More and more patients are getting ibrutinib—or other BTK [Bruton tyrosine kinase] inhibitors—earlier, as they have become FDA approved.

I’m seeing very few patients who are getting chemotherapy in the frontline and second line and then being referred into our center for other therapies. These patients are coming in being exposed to at least a BTK inhibitor, and in some situations also venetoclax, a BCL2 inhibitor, prior to being referred to us for refractory disease.

In that sense, that’s really impacted how we conduct our clinical trials. Because of previous exposure, these patients have seen what they’ll be eligible for moving forward. Overall, we know that some of these BTK-refractory patients—not just those who are intolerant, but the refractory patients—are a very tough group of patients to treat.

I’m sure everybody else on the panel can also suggest that and discuss it. I struggle a lot trying to manage these patients. I don’t know a good way to get a durable response. Anything we can get in this patient group will be important. And I think some of the information with these cellular therapies, and even these bispecific antibodies, will be important because chemotherapy hasn’t worked. With some of the other FDA-approved agents, such as bortezomib and lenalidomide, I haven’t had any durability of response.

Ian Flinn, MD: It is amazing if you step back and you think about where we were 20 years ago when the literature suggested that, in natural history of this disease, there was a 3-year median survival. Now it’s clearly much longer.

Maybe there’s not any 1 thing. Maybe it’s multiple different contributions. Clearly, frontline therapy is changing. It’s better. We’re getting deeper, longer remissions, and then from the second-line therapy, things are also changing dramatically.

Javier, do you think that chemoimmunotherapy is dead in the second line? Is there ever a case to be made for using that? It’s hard to be completely dogmatic, but what do you think?

Javier Munoz, MD, FACP: It’s a good point, and I think that in the communities, some of our colleagues are still using chemotherapy. Again, when you have a hammer, everything looks like a nail. I believe this is because of knowledge when it comes to other lymphoproliferative disorders. People are used to prescribing bendamustine-rituximab for follicular lymphoma and chronic lymphocytic leukemia. They prescribe R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone] for diffuse large B-cell lymphoma.

When they have a patient with mantle cell lymphoma who just keeps recurring, sometimes it’s tempting to keep prescribing chemotherapies. My take-home message is: try to shy away from chemotherapy as much as possible in second-line therapy, or subsequent therapies, and think about novel agents. Think about clinical trials.


Transcript Edited for Clarity 

 

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Transcript: 

Ian Flinn, MD:
Let’s move beyond first-line therapy for patients with mantle cell lymphoma. Tycel, the landscape is changing. What’s your take on things?

Tycel Jovelle Phillips, MD: Chemotherapy is not really preferred. With more and more of these novel drugs coming out, and especially with the more recent data that Simon Rule has presented on long-term outcomes with ibrutinib in first relapse, my experience has reflected itself in my patient population. More and more patients are getting ibrutinib—or other BTK [Bruton tyrosine kinase] inhibitors—earlier, as they have become FDA approved.

I’m seeing very few patients who are getting chemotherapy in the frontline and second line and then being referred into our center for other therapies. These patients are coming in being exposed to at least a BTK inhibitor, and in some situations also venetoclax, a BCL2 inhibitor, prior to being referred to us for refractory disease.

In that sense, that’s really impacted how we conduct our clinical trials. Because of previous exposure, these patients have seen what they’ll be eligible for moving forward. Overall, we know that some of these BTK-refractory patients—not just those who are intolerant, but the refractory patients—are a very tough group of patients to treat.

I’m sure everybody else on the panel can also suggest that and discuss it. I struggle a lot trying to manage these patients. I don’t know a good way to get a durable response. Anything we can get in this patient group will be important. And I think some of the information with these cellular therapies, and even these bispecific antibodies, will be important because chemotherapy hasn’t worked. With some of the other FDA-approved agents, such as bortezomib and lenalidomide, I haven’t had any durability of response.

Ian Flinn, MD: It is amazing if you step back and you think about where we were 20 years ago when the literature suggested that, in natural history of this disease, there was a 3-year median survival. Now it’s clearly much longer.

Maybe there’s not any 1 thing. Maybe it’s multiple different contributions. Clearly, frontline therapy is changing. It’s better. We’re getting deeper, longer remissions, and then from the second-line therapy, things are also changing dramatically.

Javier, do you think that chemoimmunotherapy is dead in the second line? Is there ever a case to be made for using that? It’s hard to be completely dogmatic, but what do you think?

Javier Munoz, MD, FACP: It’s a good point, and I think that in the communities, some of our colleagues are still using chemotherapy. Again, when you have a hammer, everything looks like a nail. I believe this is because of knowledge when it comes to other lymphoproliferative disorders. People are used to prescribing bendamustine-rituximab for follicular lymphoma and chronic lymphocytic leukemia. They prescribe R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone] for diffuse large B-cell lymphoma.

When they have a patient with mantle cell lymphoma who just keeps recurring, sometimes it’s tempting to keep prescribing chemotherapies. My take-home message is: try to shy away from chemotherapy as much as possible in second-line therapy, or subsequent therapies, and think about novel agents. Think about clinical trials.


Transcript Edited for Clarity 

 
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