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Flinn Highlights Emerging Combinations in CLL

Danielle Bucco
Published: Monday, Feb 26, 2018

Ian W. Flinn, MD, PhD
Ian W. Flinn, MD, PhD
Several promising combinations are being investigated for patients with chronic lymphocytic leukemia (CLL), according to Ian W. Flinn, MD, citing a number of ongoing trials presented at the 2017 ASH Annual Meeting.

on Hematologic Malignancies, Flinn, director of the Blood Cancer Research Program at Sarah Cannon Research Institute, discussed ongoing advances with emerging combination regimens in CLL.

OncLive®: What recent advances have we seen in CLL?

Flinn: There are changes in the way we are treating patients with CLL. We now have the wonderful advancement of BTK inhibitors, such as ibrutinib (Imbruvica). Patients will stay on these therapies indefinitely, which has changed the natural history of the disease. We are moving the field along and are developing combination regimens.

We are still unsure of what the right regimen is. There are many different doublets and triplets, making it hard to determine which regimen will be most beneficial. The sequencing of these agents is an additional challenge.

Please expand on the challenge of selecting the best regimen for each patient.

That is an important question. At this point, we do not know [which combination is optimal for which patient]. We know that combination therapy works broadly in the high-risk patient populations as we are seeing deep remissions, but we are not sure if the patients with low-risk disease need the same combinations. These combinations are expensive and perhaps we can dial it down in some patient populations. However, we are at a starting point where we are getting patients into MRD-negative complete remissions that we have never seen before.

A remaining question is, “Do you need to combine ibrutinib with rituximab?” In the early developmental days of ibrutinib and other B-cell receptor pathway drugs, we saw tremendous lymphocytosis occur, which was frightening to some patients and doctors. The question is whether we should add an anti-CD20 agent with that combination.

There were data presented at the 2017 ASH Annual Meeting that suggested this might not be helpful. The group at The University of Texas MD Anderson Cancer Center did a randomized trial in the relapsed and frontline setting where patients received ibrutinib alone, whereas the other half received ibrutinib with rituximab. Unfortunately, the rituximab combination did not add anything in this setting. CD20 is important with venetoclax combinations but there are no dramatic differences with ibrutinib combinations. In that study, there was no difference in PFS or OS.

Will the field be moving into triplet regimens?

Those studies are currently ongoing. We saw data from Dr Kerry Rogers of The Ohio State Comprehensive Cancer Center that was looking at a triplet regimen. These are exciting data, but it is hard to read since these studies investigated small numbers of patients in each of the high-risk subgroups. It is unclear what to do.

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