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Venetoclax-Based Regimens as First-Line Therapy in CLL

Panelists: Matthew S. Davids, MD, MMSc Dana-Farber Cancer Institute; Naval G. Daver, MD The University of Texas MD Anderson Cancer Center; Daniel A. Pollyea, MD, MS University of Colorado School of Medicine
Published: Friday, Jan 25, 2019



Transcript:

Matthew S. Davids, MD, MMSc:
Venetoclax has now been FDA approved for patients with relapsed and refractory CLL[chronic lymphocytic leukemia]. But a big question in the field is, how efficacious will a venetoclax-based regimen in the front-line setting as an initial treatment? And fortunately this is now being explored in a large randomized phase III trial called CLL14, which is randomizing previously untreated older CLL patients to either a standard regimen, chlorambucil with obinutuzumab, or the experimental regimen, venetoclax with obinutuzumab.

The design of this study is such that the venetoclax-obinutuzumab regimen is given as a 1-year time-limited regimen. And we’ve seen, now, a press release that says that there’s a progression-free survival benefit of the venetoclax-obinutuzumab regimen over chlorambucil with obinutuzumab. However, we have not see the rest of the data of this study other than a brief safety lead-in that was published last year. And so we eagerly await the results of the larger data set of this full trial to see how effective and well tolerated this regimen may be.

I think the significance of a 12-month regimen is that if that’s a way that we can get patients into a deep remission and allow for a treatment holiday of hopefully at least a few years, that would be a major advance, particularly as we think about comparing that to, for example, BTK [Bruton tyrosine kinase] inhibitors, which require continuous ongoing therapy. However, we really need to see the data before we can make that assumption, and I think right now the jury is still out as to whether 1 year is enough therapy and whether we need more of a strategy that’s guided by MRD [minimal residual disease] status where patients may need varying lengths of therapy depending on how long it takes them to get to MRD, and then discontinue at that time point.

If the CLL14 study is positive, as we expect it to be, and the venetoclax plus obinutuzumab’s 1-year time limited regimen is feasible, I think that could have a major impact on how we treat patients with CLL in the front-line setting. I think the biggest impact may be in patients who have high-risk CLL such as deletion 17p or TP53 mutation. Because right now really the only treatment option we have for these patients is ibrutinib. And if venetoclax gets a label in the frontline setting, then we’ll have another option for these patients, and I think that’s always good for patients to have these options.

Venetoclax with obinutuzumab may also be a good option for patients without deletion 17p. And so I think it’s going to be a regimen that has a lot of potential for many patients with CLL, particularly if this 1-year time-limited therapy does prove to be feasible.

Transcript edited for clarity.
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Transcript:

Matthew S. Davids, MD, MMSc:
Venetoclax has now been FDA approved for patients with relapsed and refractory CLL[chronic lymphocytic leukemia]. But a big question in the field is, how efficacious will a venetoclax-based regimen in the front-line setting as an initial treatment? And fortunately this is now being explored in a large randomized phase III trial called CLL14, which is randomizing previously untreated older CLL patients to either a standard regimen, chlorambucil with obinutuzumab, or the experimental regimen, venetoclax with obinutuzumab.

The design of this study is such that the venetoclax-obinutuzumab regimen is given as a 1-year time-limited regimen. And we’ve seen, now, a press release that says that there’s a progression-free survival benefit of the venetoclax-obinutuzumab regimen over chlorambucil with obinutuzumab. However, we have not see the rest of the data of this study other than a brief safety lead-in that was published last year. And so we eagerly await the results of the larger data set of this full trial to see how effective and well tolerated this regimen may be.

I think the significance of a 12-month regimen is that if that’s a way that we can get patients into a deep remission and allow for a treatment holiday of hopefully at least a few years, that would be a major advance, particularly as we think about comparing that to, for example, BTK [Bruton tyrosine kinase] inhibitors, which require continuous ongoing therapy. However, we really need to see the data before we can make that assumption, and I think right now the jury is still out as to whether 1 year is enough therapy and whether we need more of a strategy that’s guided by MRD [minimal residual disease] status where patients may need varying lengths of therapy depending on how long it takes them to get to MRD, and then discontinue at that time point.

If the CLL14 study is positive, as we expect it to be, and the venetoclax plus obinutuzumab’s 1-year time limited regimen is feasible, I think that could have a major impact on how we treat patients with CLL in the front-line setting. I think the biggest impact may be in patients who have high-risk CLL such as deletion 17p or TP53 mutation. Because right now really the only treatment option we have for these patients is ibrutinib. And if venetoclax gets a label in the frontline setting, then we’ll have another option for these patients, and I think that’s always good for patients to have these options.

Venetoclax with obinutuzumab may also be a good option for patients without deletion 17p. And so I think it’s going to be a regimen that has a lot of potential for many patients with CLL, particularly if this 1-year time-limited therapy does prove to be feasible.

Transcript edited for clarity.
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