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Options for Upfront Therapy in MCL

Insights From: Brad Kahl, MD, Washington University School of Medicine; John P. Leonard, MD, Weill Cornell Medical Center
Published: Tuesday, Aug 29, 2017


Transcript:

John P. Leonard, MD: There is a role for “watch and wait” in some patients with mantle cell lymphoma, similarly to how we watch and wait, or observe patients with follicular and other indolent lymphomas. That’s something that Peter Martin in our group first established. We approach mantle cell lymphoma as we do with indolent lymphomas. If the patient has low tumor burden disease, minimal symptoms, no major lab abnormalities, or no impending organ problems, in general we would assess those patients and if they didn’t have an otherwise clear need for treatment, we would observe those patients. And it turns out that there is a group of patients, and I would say a minority of patients, probably somewhere in the range of one-quarter of patients with mantle cell, where it’s reasonable to watch for a period of time. It turns out that outcomes with those patients are that they actually do better than other patients. Now, that’s not a fair comparison because those are obviously the patients who have the best disease, they’re not very sick. But there are several other studies that have confirmed our findings that there appears to be no downside to watch and wait in patients with mantle cell.

Now, you can look at this again by the clinical criteria—not bulky disease, normal labs, no symptoms. Some would argue that a low Ki-67 might say that it is more reasonable to do a watch-and-wait approach. There’s also a subset of patients who present with a CLL-type of mantle cell lymphoma with a high white cell count, bone marrow involvement, splenic involvement, but less nodal disease, and those may be patients who have a more indolent course where “watch and wait” might be reasonable, as well.

Brad S. Kahl, MD: When we have a patient with mantle cell lymphoma who requires treatment, typically we’re looking at different kinds of immunochemotherapy as the frontline treatment option. And really what I do in my practice is look at the patient, their age, their comorbidities, and talk about goals of therapy because there really isn’t a standard frontline treatment. There are several reasonable options for frontline treatment, and you really have to discuss the trade-offs between the different strategies with the patient.

Historically, R-CHOP was a very common regimen for frontline mantle cell lymphoma, but outcomes are really not that terrific with simple R-CHOP chemotherapy. Maintenance rituximab added to R-CHOP chemotherapy does improve outcomes, but what we’ve learned more recently is that the BR regimen, bendamustine and rituximab, seems to outperform R-CHOP in a couple of different head-to-head trials. So, for older mantle cell patients, the data would suggest that BR is a better immunochemotherapy platform as a standard option. For younger patients, you have the option of giving more intensive treatment strategies. Older patients really can’t tolerate those types of strategies. Examples of intensive treatment strategies would be regimens that include high-dose cytarabine in the induction part, and these regimens are often incorporated with autologous stem cell transplantation. So, as part of a package, patients will go through an induction course and then stem cells are collected and then they receive an autologous stem cell transplant on the back end of that treatment program.

A commonly used regimen is called Nordic, another highly effective regimen R-CHOP with a chemotherapy regimen called R-DHAP, and that’s commonly used in Europe. And regimens that use that paradigm, high-dose cytarabine in the induction with autologous stem cell transplant, generally produce average remissions exceeding 7 years. And so, those are very good outcomes for frontline mantle cell lymphoma treatment.

Mantle cell lymphoma is actually very responsive to radiation treatment. The problem is that mantle cell lymphoma is typically widespread in most patients, and radiation only works where you point the beam. And so, to use radiation therapy for someone with advanced stage disease rarely comes into play. It’s just not the most useful tool. But if you do have a patient with limited stage mantle cell lymphoma—which is rare but it does happen—or you have a patient with advanced stage disease but they just have one problem area, like a big lymph node in one spot that’s giving them pain or other symptoms, radiation can be a very useful tool for disease management in those scenarios.

Transcript Edited for Clarity
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Transcript:

John P. Leonard, MD: There is a role for “watch and wait” in some patients with mantle cell lymphoma, similarly to how we watch and wait, or observe patients with follicular and other indolent lymphomas. That’s something that Peter Martin in our group first established. We approach mantle cell lymphoma as we do with indolent lymphomas. If the patient has low tumor burden disease, minimal symptoms, no major lab abnormalities, or no impending organ problems, in general we would assess those patients and if they didn’t have an otherwise clear need for treatment, we would observe those patients. And it turns out that there is a group of patients, and I would say a minority of patients, probably somewhere in the range of one-quarter of patients with mantle cell, where it’s reasonable to watch for a period of time. It turns out that outcomes with those patients are that they actually do better than other patients. Now, that’s not a fair comparison because those are obviously the patients who have the best disease, they’re not very sick. But there are several other studies that have confirmed our findings that there appears to be no downside to watch and wait in patients with mantle cell.

Now, you can look at this again by the clinical criteria—not bulky disease, normal labs, no symptoms. Some would argue that a low Ki-67 might say that it is more reasonable to do a watch-and-wait approach. There’s also a subset of patients who present with a CLL-type of mantle cell lymphoma with a high white cell count, bone marrow involvement, splenic involvement, but less nodal disease, and those may be patients who have a more indolent course where “watch and wait” might be reasonable, as well.

Brad S. Kahl, MD: When we have a patient with mantle cell lymphoma who requires treatment, typically we’re looking at different kinds of immunochemotherapy as the frontline treatment option. And really what I do in my practice is look at the patient, their age, their comorbidities, and talk about goals of therapy because there really isn’t a standard frontline treatment. There are several reasonable options for frontline treatment, and you really have to discuss the trade-offs between the different strategies with the patient.

Historically, R-CHOP was a very common regimen for frontline mantle cell lymphoma, but outcomes are really not that terrific with simple R-CHOP chemotherapy. Maintenance rituximab added to R-CHOP chemotherapy does improve outcomes, but what we’ve learned more recently is that the BR regimen, bendamustine and rituximab, seems to outperform R-CHOP in a couple of different head-to-head trials. So, for older mantle cell patients, the data would suggest that BR is a better immunochemotherapy platform as a standard option. For younger patients, you have the option of giving more intensive treatment strategies. Older patients really can’t tolerate those types of strategies. Examples of intensive treatment strategies would be regimens that include high-dose cytarabine in the induction part, and these regimens are often incorporated with autologous stem cell transplantation. So, as part of a package, patients will go through an induction course and then stem cells are collected and then they receive an autologous stem cell transplant on the back end of that treatment program.

A commonly used regimen is called Nordic, another highly effective regimen R-CHOP with a chemotherapy regimen called R-DHAP, and that’s commonly used in Europe. And regimens that use that paradigm, high-dose cytarabine in the induction with autologous stem cell transplant, generally produce average remissions exceeding 7 years. And so, those are very good outcomes for frontline mantle cell lymphoma treatment.

Mantle cell lymphoma is actually very responsive to radiation treatment. The problem is that mantle cell lymphoma is typically widespread in most patients, and radiation only works where you point the beam. And so, to use radiation therapy for someone with advanced stage disease rarely comes into play. It’s just not the most useful tool. But if you do have a patient with limited stage mantle cell lymphoma—which is rare but it does happen—or you have a patient with advanced stage disease but they just have one problem area, like a big lymph node in one spot that’s giving them pain or other symptoms, radiation can be a very useful tool for disease management in those scenarios.

Transcript Edited for Clarity
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