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The Role of Maintenance Therapy in CLL

Panelists: Krishna V. Komanduri, MD, Sylvester Comprehensive Cancer Center; Leo I. Gordon, MD, Robert H. Lurie Comprehensive Cancer Center; John Byrd, MD, Ohio State University; Michael Keating, MB, BS, University of Texas MD Anderson Cancer Center; John Leonard, MD, New York-Presbyterian Hospital
Published: Wednesday, Feb 08, 2017



Transcript:

Krishna V. Komanduri, MD:
Michael, I think you highlighted some of the parallels there between the low-grade lymphoma discussion we just had and CLL. And certainly, one of the things that I think is a canonical theme in almost every area of hematology, including acute leukemia therapy and post-stem cell transplant setting, is now the role of maintenance therapies. So, we have new data building on old data on the role of maintenance with either lenalidomide or rituximab. Can you comment on your thoughts about those studies?

Michael J. Keating, MB, BS: I think it’s really interesting. The Germans have looked at the study and the patients on it that are at high-risk of failing and that hadn’t achieved MRD negativity, and looked at lenalidomide versus observation. There was quite a marked improvement in progression-free survival in that circumstance. Now whether it does translate into an overall survival outcome is questionable.

There was a concern that was first raised by the people in Barcelona with the FCMR (fludarabine, cyclophosphamide, mitoxantrone, rituximab) regimen. They had most of their patients going on to maintenance therapy, and they recommended against it now because of long-term infections that were occurring later on that were not occurring in most of the FCR studies that were reported. So, we have to realize how potent rituximab and obinutuzumab are in the B cell population, and the fact that the B cells and the T cells are not single characteristics as the interaction between the B cells and the T cells. And we know that if we mess up the B cells, we have fairly marked impacts on the T-cell population.

So, it’s nice that we have studies that are looking at this. It’s nice that lenalidomide in particular doesn’t impair the T cell function number. And my impression is that it makes their response to subsequent treatments actually better. It’s an observation that’s just anecdotal, but after you see a lot of patients, the anecdotes get bigger and bigger.

Krishna V. Komanduri, MD: I think, to add to your anecdote, in the post-transplant setting in myeloma, for example, we do see an increased risk of secondary malignancies. And then I think, as you talked about, that causes may be multiple. But, we don’t typically see unusual infections occurring in those patients—even those who have been on long-term lenalidomide therapy—and even in relatively early transplant, we don’t typically see CMV or pneumocystis, for example. So, I think that there isn’t really good evidence that it suppresses T cells in that way.

John Byrd, MD: No. And I think it’s because of lenalidomide. This is going to be a story because there are 2 abstracts at this meeting. There are other data that have been presented or will be coming forward. I think this is a hot area, and there are very few drugs in CLL that make the immune system normal. Jeff Jones from our institution has an early treatment study where patients who are high-risk—as Mike was referring to—received an infectious vaccine plus lenalidomide. And the notable thing about that abstract was confirming an observation that Michael’s group has made, that the majority of those patients that started with, well, immunoglobulins had normalized their immunoglobulins. There are no drugs that do that, and while we’ve seen some patients progress on that study, it’s been very small. Even the patients that have progressed that have gone off when we stopped the lenalidomide, we’ve had a number of patients that have had very durable stable disease where you just wouldn’t have expected that. So, this is a drug that’s, with all the new things, shoved to the side a little bit, and it’s going to be interesting to see how it integrates in with some of the targeted therapies.

Transcript Edited for Clarity

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Transcript:

Krishna V. Komanduri, MD:
Michael, I think you highlighted some of the parallels there between the low-grade lymphoma discussion we just had and CLL. And certainly, one of the things that I think is a canonical theme in almost every area of hematology, including acute leukemia therapy and post-stem cell transplant setting, is now the role of maintenance therapies. So, we have new data building on old data on the role of maintenance with either lenalidomide or rituximab. Can you comment on your thoughts about those studies?

Michael J. Keating, MB, BS: I think it’s really interesting. The Germans have looked at the study and the patients on it that are at high-risk of failing and that hadn’t achieved MRD negativity, and looked at lenalidomide versus observation. There was quite a marked improvement in progression-free survival in that circumstance. Now whether it does translate into an overall survival outcome is questionable.

There was a concern that was first raised by the people in Barcelona with the FCMR (fludarabine, cyclophosphamide, mitoxantrone, rituximab) regimen. They had most of their patients going on to maintenance therapy, and they recommended against it now because of long-term infections that were occurring later on that were not occurring in most of the FCR studies that were reported. So, we have to realize how potent rituximab and obinutuzumab are in the B cell population, and the fact that the B cells and the T cells are not single characteristics as the interaction between the B cells and the T cells. And we know that if we mess up the B cells, we have fairly marked impacts on the T-cell population.

So, it’s nice that we have studies that are looking at this. It’s nice that lenalidomide in particular doesn’t impair the T cell function number. And my impression is that it makes their response to subsequent treatments actually better. It’s an observation that’s just anecdotal, but after you see a lot of patients, the anecdotes get bigger and bigger.

Krishna V. Komanduri, MD: I think, to add to your anecdote, in the post-transplant setting in myeloma, for example, we do see an increased risk of secondary malignancies. And then I think, as you talked about, that causes may be multiple. But, we don’t typically see unusual infections occurring in those patients—even those who have been on long-term lenalidomide therapy—and even in relatively early transplant, we don’t typically see CMV or pneumocystis, for example. So, I think that there isn’t really good evidence that it suppresses T cells in that way.

John Byrd, MD: No. And I think it’s because of lenalidomide. This is going to be a story because there are 2 abstracts at this meeting. There are other data that have been presented or will be coming forward. I think this is a hot area, and there are very few drugs in CLL that make the immune system normal. Jeff Jones from our institution has an early treatment study where patients who are high-risk—as Mike was referring to—received an infectious vaccine plus lenalidomide. And the notable thing about that abstract was confirming an observation that Michael’s group has made, that the majority of those patients that started with, well, immunoglobulins had normalized their immunoglobulins. There are no drugs that do that, and while we’ve seen some patients progress on that study, it’s been very small. Even the patients that have progressed that have gone off when we stopped the lenalidomide, we’ve had a number of patients that have had very durable stable disease where you just wouldn’t have expected that. So, this is a drug that’s, with all the new things, shoved to the side a little bit, and it’s going to be interesting to see how it integrates in with some of the targeted therapies.

Transcript Edited for Clarity
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