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Selecting the Optimal Frontline Therapy in 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: Friday, Apr 27, 2018



Transcript: 

Michael Choi, MD: The decision to start treatment for a patient with CLL is still based on determining that the patient has symptoms, complications, or marrow dysfunction that are due to the CLL and outweigh the risks of treatment. Although there are many very promising treatments that have improved the therapeutic index, there still are not studies that conclusively show that starting treatment earlier in the course of a patient’s CLL changes the course of disease or is warranted. So, the same guidelines that were established by the International Working Groups still apply, and those are the ones I still follow today. Of course, there are trials that are ongoing to evaluate earlier initiation of drugs, like ibrutinib, and certainly I await those findings. But for most patients, I still want to make sure that the patient is going to have benefit beyond theoretical benefit in their disease.

The main first-line treatment options available now still broadly fall into the class of chemoimmunotherapy regimens or ibrutinib. For younger, fitter patients or patients who prioritize the treatment that has a defined duration, chemoimmunotherapy combinations such as FCR or BR, or some regimens that now incorporate obinutuzumab, have been shown to have very high response rates and durability of response that result in treatment-free remissions. Ibrutinib, however, has been shown to be an equally efficacious frontline option, especially for patients who are older. The duration of remission and the progression-free survival have not yet been reached. It may turn out to be that ibrutinib keeps people well for as long as some of those chemoimmunotherapy regimens.

When deciding on different treatment options in the frontline setting, there are a number of factors to consider, and that certainly leads to detailed and important discussions with our patients. Certainly, there are some biologic factors that have been established as predictive markers or that can predict the quality and duration of response. In particular, it’s now been shown that the mutation status of the immunoglobulin gene can predict the duration of remission after FCR therapy and that patients with a mutated immunoglobulin gene are the ones with a chance of having ultra-long, longer than 10 or 15 years, remissions following FCR. Certainly, cytogenetics are critical to assess before making a decision. Patients with deletion 17p will be on the opposite end of that spectrum, with very short remissions after FCR.

Beyond those factors, certainly patient factors like age, fitness, and comorbid conditions are important to take into account. With some of these agents, there are specific factors, such as risk of bleeding with ibrutinib or even cardiovascular history, which appear to correlate with the cardiovascular complications of ibrutinib. Finally, we should not understate the importance of patient preference. There are patients who are young and fit and on paper would be very appropriate for FCR but who would prefer ibrutinib, with the thought of avoiding potential toxicities, both short and long term. I don’t think that’s a wrong choice either. In this day and age, we are also confronted sometimes with cost issues, and I think that’s also something that we should take into account when helping our patients decide on their treatment.

Transcript Edited for Clarity 
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Transcript: 

Michael Choi, MD: The decision to start treatment for a patient with CLL is still based on determining that the patient has symptoms, complications, or marrow dysfunction that are due to the CLL and outweigh the risks of treatment. Although there are many very promising treatments that have improved the therapeutic index, there still are not studies that conclusively show that starting treatment earlier in the course of a patient’s CLL changes the course of disease or is warranted. So, the same guidelines that were established by the International Working Groups still apply, and those are the ones I still follow today. Of course, there are trials that are ongoing to evaluate earlier initiation of drugs, like ibrutinib, and certainly I await those findings. But for most patients, I still want to make sure that the patient is going to have benefit beyond theoretical benefit in their disease.

The main first-line treatment options available now still broadly fall into the class of chemoimmunotherapy regimens or ibrutinib. For younger, fitter patients or patients who prioritize the treatment that has a defined duration, chemoimmunotherapy combinations such as FCR or BR, or some regimens that now incorporate obinutuzumab, have been shown to have very high response rates and durability of response that result in treatment-free remissions. Ibrutinib, however, has been shown to be an equally efficacious frontline option, especially for patients who are older. The duration of remission and the progression-free survival have not yet been reached. It may turn out to be that ibrutinib keeps people well for as long as some of those chemoimmunotherapy regimens.

When deciding on different treatment options in the frontline setting, there are a number of factors to consider, and that certainly leads to detailed and important discussions with our patients. Certainly, there are some biologic factors that have been established as predictive markers or that can predict the quality and duration of response. In particular, it’s now been shown that the mutation status of the immunoglobulin gene can predict the duration of remission after FCR therapy and that patients with a mutated immunoglobulin gene are the ones with a chance of having ultra-long, longer than 10 or 15 years, remissions following FCR. Certainly, cytogenetics are critical to assess before making a decision. Patients with deletion 17p will be on the opposite end of that spectrum, with very short remissions after FCR.

Beyond those factors, certainly patient factors like age, fitness, and comorbid conditions are important to take into account. With some of these agents, there are specific factors, such as risk of bleeding with ibrutinib or even cardiovascular history, which appear to correlate with the cardiovascular complications of ibrutinib. Finally, we should not understate the importance of patient preference. There are patients who are young and fit and on paper would be very appropriate for FCR but who would prefer ibrutinib, with the thought of avoiding potential toxicities, both short and long term. I don’t think that’s a wrong choice either. In this day and age, we are also confronted sometimes with cost issues, and I think that’s also something that we should take into account when helping our patients decide on their treatment.

Transcript Edited for Clarity 
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