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The Evolving Treatment Landscape of CLL

Insights From: Michael Choi, MD, UC San Diego Medical Center; Matthew S. Davids, MD, Dana-Farber Cancer Institute; William Wierda, MD, PhD, MD Anderson Cancer Center
Published: Wednesday, May 30, 2018



Transcript: 

Matthew S. Davids, MD: One of the great things in CLL right now is that we have many new drugs and many new approaches, but that also presents a significant challenge in terms of trying to figure out what the optimal strategy for an individual patient with CLL is. Right now, especially from the recent ASH meeting, we’ve seen some very exciting phase II data of various combinations of ibrutinib (Imbruvica) and venetoclax (Venclexta), with or without antibodies. I think it’s going to be a challenge for the field to compare many different phase II studies across the board and try to determine what may be best.

Important phase III studies that have launched now, including the FLAIR trial in the United Kingdom, as well as the CLL13 [GAIA] trial in Germany, are going to help define new standards of care with a database approach from a phase III trial setting. I think it is going to be individualized for particular patients, and that’s going to depend on both the biological characteristics of the disease, meaning FISH testing or mutational profiles, and the comorbidities of the patient. We know that certain drugs are challenging for patients based on their specific comorbidities. Each patient is going to require an individualized regimen, but, hopefully, this can be guided by the data from the phase III studies as much as possible.

Michael Choi, MD: We’re fortunate that there are a number of very excellent drugs in development and recently developed to treat patients with CLL. The quality of life and the expectations for a normal life are higher than ever before, but I do think there are things that are important to patients that we haven’t achieved yet.

We want to be at a point where patients can expect to have a remission that can last even without ongoing treatment, we want treatments that do not bring with them side effects that may linger, and we want treatments or treatment regimens that can be feasible for us as a society to use without putting patients’ finances or savings at risk. I think those things are potentially within reach with some of the combinations that are being explored. I’m certainly excited to see what unfolds next.

With several treatment options now, it is a time where we already need to individualize treatment decisions for each of our patients. There is not a trial or a study that compares these. There usually isn’t 1 drug that fits every case, so I think it’s time we really need to know our patients—to know what’s important to them—and to assess not just their clinical status and the biology of the CLL cells but also their family situation and their social situation. Putting all of that together can help us individualize their treatment more. In the future, we’ll have more tools. We’ll have better knowledge of genetics or predictive factors, but we’ll always turn back to the very basic principle of listening to our patients and letting them tell us what’s important to them.

Matthew S. Davids, MD: In the 1960s and 1970s, there was a really exciting time in cancer therapy when we had all these new chemotherapy drugs that had come along primarily as single agents. Some very smart people at the National Cancer Institute began to put them together into rational combination regimens, and this is how we developed curative regimens in our field for diseases like Hodgkin lymphoma and diffused large B-cell lymphoma.

Historically, CLL has been considered an incurable disease, but we finally now have all the different tools in our armamentarium to design combination-based regimens to cure the disease. It’s exciting to explore combinations of these new drugs with the older chemotherapy regimens, combinations of the new drugs with each other, and combinations with the CD20 antibodies. I am optimistic that by doing some smart clinical trials over a period of time, we are going to be able to define curative regimens for patients with this disease. I’m certainly very optimistic about the future of CLL therapy.

Transcript Edited for Clarity 
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Transcript: 

Matthew S. Davids, MD: One of the great things in CLL right now is that we have many new drugs and many new approaches, but that also presents a significant challenge in terms of trying to figure out what the optimal strategy for an individual patient with CLL is. Right now, especially from the recent ASH meeting, we’ve seen some very exciting phase II data of various combinations of ibrutinib (Imbruvica) and venetoclax (Venclexta), with or without antibodies. I think it’s going to be a challenge for the field to compare many different phase II studies across the board and try to determine what may be best.

Important phase III studies that have launched now, including the FLAIR trial in the United Kingdom, as well as the CLL13 [GAIA] trial in Germany, are going to help define new standards of care with a database approach from a phase III trial setting. I think it is going to be individualized for particular patients, and that’s going to depend on both the biological characteristics of the disease, meaning FISH testing or mutational profiles, and the comorbidities of the patient. We know that certain drugs are challenging for patients based on their specific comorbidities. Each patient is going to require an individualized regimen, but, hopefully, this can be guided by the data from the phase III studies as much as possible.

Michael Choi, MD: We’re fortunate that there are a number of very excellent drugs in development and recently developed to treat patients with CLL. The quality of life and the expectations for a normal life are higher than ever before, but I do think there are things that are important to patients that we haven’t achieved yet.

We want to be at a point where patients can expect to have a remission that can last even without ongoing treatment, we want treatments that do not bring with them side effects that may linger, and we want treatments or treatment regimens that can be feasible for us as a society to use without putting patients’ finances or savings at risk. I think those things are potentially within reach with some of the combinations that are being explored. I’m certainly excited to see what unfolds next.

With several treatment options now, it is a time where we already need to individualize treatment decisions for each of our patients. There is not a trial or a study that compares these. There usually isn’t 1 drug that fits every case, so I think it’s time we really need to know our patients—to know what’s important to them—and to assess not just their clinical status and the biology of the CLL cells but also their family situation and their social situation. Putting all of that together can help us individualize their treatment more. In the future, we’ll have more tools. We’ll have better knowledge of genetics or predictive factors, but we’ll always turn back to the very basic principle of listening to our patients and letting them tell us what’s important to them.

Matthew S. Davids, MD: In the 1960s and 1970s, there was a really exciting time in cancer therapy when we had all these new chemotherapy drugs that had come along primarily as single agents. Some very smart people at the National Cancer Institute began to put them together into rational combination regimens, and this is how we developed curative regimens in our field for diseases like Hodgkin lymphoma and diffused large B-cell lymphoma.

Historically, CLL has been considered an incurable disease, but we finally now have all the different tools in our armamentarium to design combination-based regimens to cure the disease. It’s exciting to explore combinations of these new drugs with the older chemotherapy regimens, combinations of the new drugs with each other, and combinations with the CD20 antibodies. I am optimistic that by doing some smart clinical trials over a period of time, we are going to be able to define curative regimens for patients with this disease. I’m certainly very optimistic about the future of CLL therapy.

Transcript Edited for Clarity 
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