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Evaluating Pharmacologic Agents in Relapsed/Refractory 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 16, 2018



Transcript: 

Michael Choi, MD: Factors that I consider when selecting ibrutinib for a patient would largely be focused on the potential adverse effects or toxicities of ibrutinib. Patients who are at high risk for bleeding, perhaps due to prior bleeding events; thrombocytopenia; or the need to be on anticoagulant medications are considerations. Cardiovascular history, or a history of atrial fibrillation, is also a consideration. There is a published track record of treating patients with these factors safely with ibrutinib, but I do suppose if there are other treatment options, that it is a consideration. Part of the main factor with ibrutinib is that patients should understand it is a drug that is meant to be continued in the long-term. It’s not that they are trapped on the drug, but it is given with the knowledge that the drug is effective so long as it’s taken and that disease does tend to relapse fairly soon after it’s stopped. Perhaps patients who are more inclined for a shorter treatment duration would be less appropriate for ibrutinib.

Dose-dense rituximab is an active agent for patients with CLL, but with the development of novel targeted agents like ibrutinib, idelalisib, and venetoclax, I do think it’s not something that I intend to turn to first. Specifically, some of the main trials were designed as a direct comparison against rituximab, such as idelalisib plus rituximab versus rituximab alone. That being said, there are patients who perhaps do not have good access to oral therapies. In my mind, patients who have autoimmune complications such as ITP [idiopathic thrombocytopenic purpura] or an autoimmune hemolysis as the main manifestation of CLL are appropriate for rituximab as a treatment option. At the very least, it can be something that stabilizes the disease or bridges a gap to receiving other therapy.

Idelalisib and rituximab were shown to be superior to rituximab alone as far as efficacy, progression-free survival, and overall survival. Certainly, it is an active regimen. There are some adverse effects that have limited its use, including colitis and other inflammatory complications. I do think patients who are starting this should be carefully counseled about those risks and reminded to alert their physicians and their teams of any new adverse effects. It is a drug that is active though, and it should be presented to patients as a treatment option, particularly those maybe having problems or contraindications to using other drugs.

At the most recent ASH [American Society of Hematology] meeting, a late-breaking abstract showed the efficacy of venetoclax in combination to be superior to bendamustine and rituximab in the relapsed/refractory setting. Similarly, previous studies have shown the efficacy of single-agent venetoclax in patients with deletion 17p, which is in its current FDA approved label. Based on that, venetoclax is a very good option for patients, especially those with 17p deletion.

A factor that is important to consider for patients, though, is the need for close monitoring of tumor lysis syndrome. For that reason, perhaps it’s not the optimal option for patients who live far from their laboratories or for patients with compromised renal function. I do think patients are drawn to this regimen, particularly the combination with rituximab, because it’s designed to be a regimen that is of a defined treatment duration and that is expected to be followed by a treatment-free remission.

The combination of lenalidomide and rituximab was studied in CLL even before it was studied in other lymphomas, where it had more attraction. Dr. Alessandra Ferrajoli and her colleagues at MD Anderson, and also Dr [Danelle] James in our group at UCSD [University of California, San Diego] in the CLL Research Consortium, studied this combination as treatment for patients with relapsed disease and even as frontline treatment. We did observe excellent efficacy and high response rates, and anecdotally, I still have patients who are continuing on lenalidomide several years later. There are some unique features of lenalidomide, including a risk of tumor flare reaction and a risk of thrombosis that I think require some attention from the treating physician. But I think it is important to remember that it is also an option. I think the access to lenalidomide now, at least in the United States, to treat patients with CLL is a little bit more difficult, particularly with the development of other agents. I think with patients for whom you don’t have other options, it is a consideration.

Transcript Edited for Clarity 
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Transcript: 

Michael Choi, MD: Factors that I consider when selecting ibrutinib for a patient would largely be focused on the potential adverse effects or toxicities of ibrutinib. Patients who are at high risk for bleeding, perhaps due to prior bleeding events; thrombocytopenia; or the need to be on anticoagulant medications are considerations. Cardiovascular history, or a history of atrial fibrillation, is also a consideration. There is a published track record of treating patients with these factors safely with ibrutinib, but I do suppose if there are other treatment options, that it is a consideration. Part of the main factor with ibrutinib is that patients should understand it is a drug that is meant to be continued in the long-term. It’s not that they are trapped on the drug, but it is given with the knowledge that the drug is effective so long as it’s taken and that disease does tend to relapse fairly soon after it’s stopped. Perhaps patients who are more inclined for a shorter treatment duration would be less appropriate for ibrutinib.

Dose-dense rituximab is an active agent for patients with CLL, but with the development of novel targeted agents like ibrutinib, idelalisib, and venetoclax, I do think it’s not something that I intend to turn to first. Specifically, some of the main trials were designed as a direct comparison against rituximab, such as idelalisib plus rituximab versus rituximab alone. That being said, there are patients who perhaps do not have good access to oral therapies. In my mind, patients who have autoimmune complications such as ITP [idiopathic thrombocytopenic purpura] or an autoimmune hemolysis as the main manifestation of CLL are appropriate for rituximab as a treatment option. At the very least, it can be something that stabilizes the disease or bridges a gap to receiving other therapy.

Idelalisib and rituximab were shown to be superior to rituximab alone as far as efficacy, progression-free survival, and overall survival. Certainly, it is an active regimen. There are some adverse effects that have limited its use, including colitis and other inflammatory complications. I do think patients who are starting this should be carefully counseled about those risks and reminded to alert their physicians and their teams of any new adverse effects. It is a drug that is active though, and it should be presented to patients as a treatment option, particularly those maybe having problems or contraindications to using other drugs.

At the most recent ASH [American Society of Hematology] meeting, a late-breaking abstract showed the efficacy of venetoclax in combination to be superior to bendamustine and rituximab in the relapsed/refractory setting. Similarly, previous studies have shown the efficacy of single-agent venetoclax in patients with deletion 17p, which is in its current FDA approved label. Based on that, venetoclax is a very good option for patients, especially those with 17p deletion.

A factor that is important to consider for patients, though, is the need for close monitoring of tumor lysis syndrome. For that reason, perhaps it’s not the optimal option for patients who live far from their laboratories or for patients with compromised renal function. I do think patients are drawn to this regimen, particularly the combination with rituximab, because it’s designed to be a regimen that is of a defined treatment duration and that is expected to be followed by a treatment-free remission.

The combination of lenalidomide and rituximab was studied in CLL even before it was studied in other lymphomas, where it had more attraction. Dr. Alessandra Ferrajoli and her colleagues at MD Anderson, and also Dr [Danelle] James in our group at UCSD [University of California, San Diego] in the CLL Research Consortium, studied this combination as treatment for patients with relapsed disease and even as frontline treatment. We did observe excellent efficacy and high response rates, and anecdotally, I still have patients who are continuing on lenalidomide several years later. There are some unique features of lenalidomide, including a risk of tumor flare reaction and a risk of thrombosis that I think require some attention from the treating physician. But I think it is important to remember that it is also an option. I think the access to lenalidomide now, at least in the United States, to treat patients with CLL is a little bit more difficult, particularly with the development of other agents. I think with patients for whom you don’t have other options, it is a consideration.

Transcript Edited for Clarity 
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