ONCAlert | Upfront Therapy for mRCC

Case 2: Choosing Treatment for CLL With Del(17p)

Targeted Oncology
Published Online:1:50 PM, Tue February 4, 2020


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: I think more and more we’ll be seeing trials where decisions are made based on depth of response rather than sort of 1-size-fits-all fixed duration. We’ve skirted around the issue with this patient. Still have to make a decision. How do we decide whether this patient gets venetoclax-obinutuzumab fixed duration or they goes on a continuous therapy with a BTK [Bruton tyrosine kinase] inhibitor?

Shuo Ma, MD, PhD: That’s becoming 1 of the most common discussions nowadays when I see my patients. So how would you make your decision...

Anthony Mato, MD, MSCE: I think the temptation to make head-to-head comparisons between venetoclax and ibrutinib for a 17p-deleted patient is tempting, but it’s also probably fraught with potentially wrong information or misinformation. We don’t have a head-to-head comparison in the frontline setting. We have very limited information about del(17p)-treated patients in the frontline setting. We mentioned 31 patients treated at a single center. There was a small number of patients treated on CLL14 with a deletion 17p, which seemed to have a worse outcome than the rest of the patients who received venetoclax. I view it as they are similar therapies for patients. I have heard talk about the fact that when you have a high-risk clone, you need to continuously suppress it and not stop therapy versus a fixed duration. I think all that is speculative research at this time and certainly unanswered.

I personally take into account patients’ age to a certain extent, their comorbidities, and their lifestyle, because each of these treatments has advantages and disadvantages that really need to be considered in the context of an individual patient. For me, I discuss it with a patient and have them actively participate in the decision of what to do. I don’t think biologically we have any firm data to support whether we need a BTK inhibitor, a BCL2 inhibitor, or both in a patient with a deletion 17p.

Shuo Ma, MD, PhD: Sameer, you have any input on when you’re discussing with a patient this class of treatments?

Sameer A. Parikh, MBBS: I think those discussions have gotten longer with all these data, which is very good for our patients, because it means that we have a lot of choices to discuss with our patients. And I agree, it is a very individualized decision, and we should refrain from making head-to-head comparisons between cross-trials because it’s challenging.

Anthony Mato, MD, MSCE: Especially with small numbers.

Sameer A. Parikh, MBBS: With very small numbers of patients. One thing that’s very reassuring—with the venetoclax-based therapies at least—is that in the past we have seen patients responding to the introduction of venetoclax if they have progression of disease. Whether that holds true for a patient who has deletion 17p, I don’t think we really know the answer to that question. I would actually put in a plug for all our patients to hopefully participate in a clinical trial. Outside a clinical trial, it’s sort of routine practice, because then we can answer many of these questions that we don’t really have good answers to. There are national ECOG- and Alliance-run trials that are enrolling patients right now, although the ECOG trial is not enrolling patients that have deletion 17p for frontline setting. I’m sure there are other trials that have patients that have deletion 17p in them as an inclusion criteria. I encourage patients and their physicians to consider enrolling patients in the clinical trials.

Shuo Ma, MD, PhD: Both of you were emphasizing the efficacy, and we don’t really know. It looks like the efficacy—at least right now—is pretty comparable. If you put deletion 17p aside, if you’re talking with a frontline patient who needs treatment between a BTK inhibitor and venetoclax, for me the breaking point is more along the lines of toxicity—consideration of toxicity and not patient lifestyle and patient preference.

For example, if a patient has a significant cardiac history, I’ll be very hesitant to use ibrutinib, the first-generation BTK inhibitor. I might be leaning more toward a venetoclax treatment. Or if patient has a significant renal insufficiency and concern about their ability to handle tumor lysis syndrome, I might lean away from the venetoclax-based therapy. For most patients, they might be eligible for both. In that case, I think a lot of the patient preference will come in. For example, some patients will say, “I like it easy, so basically I like not to interrupt my work schedule. I don’t want to be in a clinic for a full day or weekly.” Those patients might prefer to use a BTK inhibitor versus a patient who is willing to invest in up-front time, but then they might be able to stop treatment after 12 months. In those patients who they might be benefiting more from the venetoclax-based therapy. A lot of times patient preference will play into the decision making as well.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: I think more and more we’ll be seeing trials where decisions are made based on depth of response rather than sort of 1-size-fits-all fixed duration. We’ve skirted around the issue with this patient. Still have to make a decision. How do we decide whether this patient gets venetoclax-obinutuzumab fixed duration or they goes on a continuous therapy with a BTK [Bruton tyrosine kinase] inhibitor?

Shuo Ma, MD, PhD: That’s becoming 1 of the most common discussions nowadays when I see my patients. So how would you make your decision...

Anthony Mato, MD, MSCE: I think the temptation to make head-to-head comparisons between venetoclax and ibrutinib for a 17p-deleted patient is tempting, but it’s also probably fraught with potentially wrong information or misinformation. We don’t have a head-to-head comparison in the frontline setting. We have very limited information about del(17p)-treated patients in the frontline setting. We mentioned 31 patients treated at a single center. There was a small number of patients treated on CLL14 with a deletion 17p, which seemed to have a worse outcome than the rest of the patients who received venetoclax. I view it as they are similar therapies for patients. I have heard talk about the fact that when you have a high-risk clone, you need to continuously suppress it and not stop therapy versus a fixed duration. I think all that is speculative research at this time and certainly unanswered.

I personally take into account patients’ age to a certain extent, their comorbidities, and their lifestyle, because each of these treatments has advantages and disadvantages that really need to be considered in the context of an individual patient. For me, I discuss it with a patient and have them actively participate in the decision of what to do. I don’t think biologically we have any firm data to support whether we need a BTK inhibitor, a BCL2 inhibitor, or both in a patient with a deletion 17p.

Shuo Ma, MD, PhD: Sameer, you have any input on when you’re discussing with a patient this class of treatments?

Sameer A. Parikh, MBBS: I think those discussions have gotten longer with all these data, which is very good for our patients, because it means that we have a lot of choices to discuss with our patients. And I agree, it is a very individualized decision, and we should refrain from making head-to-head comparisons between cross-trials because it’s challenging.

Anthony Mato, MD, MSCE: Especially with small numbers.

Sameer A. Parikh, MBBS: With very small numbers of patients. One thing that’s very reassuring—with the venetoclax-based therapies at least—is that in the past we have seen patients responding to the introduction of venetoclax if they have progression of disease. Whether that holds true for a patient who has deletion 17p, I don’t think we really know the answer to that question. I would actually put in a plug for all our patients to hopefully participate in a clinical trial. Outside a clinical trial, it’s sort of routine practice, because then we can answer many of these questions that we don’t really have good answers to. There are national ECOG- and Alliance-run trials that are enrolling patients right now, although the ECOG trial is not enrolling patients that have deletion 17p for frontline setting. I’m sure there are other trials that have patients that have deletion 17p in them as an inclusion criteria. I encourage patients and their physicians to consider enrolling patients in the clinical trials.

Shuo Ma, MD, PhD: Both of you were emphasizing the efficacy, and we don’t really know. It looks like the efficacy—at least right now—is pretty comparable. If you put deletion 17p aside, if you’re talking with a frontline patient who needs treatment between a BTK inhibitor and venetoclax, for me the breaking point is more along the lines of toxicity—consideration of toxicity and not patient lifestyle and patient preference.

For example, if a patient has a significant cardiac history, I’ll be very hesitant to use ibrutinib, the first-generation BTK inhibitor. I might be leaning more toward a venetoclax treatment. Or if patient has a significant renal insufficiency and concern about their ability to handle tumor lysis syndrome, I might lean away from the venetoclax-based therapy. For most patients, they might be eligible for both. In that case, I think a lot of the patient preference will come in. For example, some patients will say, “I like it easy, so basically I like not to interrupt my work schedule. I don’t want to be in a clinic for a full day or weekly.” Those patients might prefer to use a BTK inhibitor versus a patient who is willing to invest in up-front time, but then they might be able to stop treatment after 12 months. In those patients who they might be benefiting more from the venetoclax-based therapy. A lot of times patient preference will play into the decision making as well.

Transcript edited for clarity.
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