ONCAlert | Upfront Therapy for mRCC

Case 3: Risk Assessment And Elderly Patients with CLL

Targeted Oncology
Published Online:1:00 PM, Tue February 11, 2020


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: Some questions about this patient to consider would be, “what is the prognosis for the patient given his molecular status and his comorbidities?” How do we evaluate those sort of independently of one another but then taking them together to make a decision for the patient?  I think the molecular status is probably the lower hanging fruit. It’s sort of easier to look at those data objectively. How would you prognosticate this patient?

Nupam A. Patel, MD: From the FISH [fluorescence in situ hybridization] perspective, we don’t have any abnormalities so that’s more of a neutral kind of prognosis. The IGHV [immunoglobulin heavy chain variable] is unmutated, and again, like we saw in previous cases, that is classically more of a poor prognosis.

Anthony Mato, MD, MSCE: Assuming we’re going to give chemotherapy.

Nupam A. Patel, MD: Exactly.

Anthony Mato, MD, MSCE: I didn’t mention whether or not this patient had next-generation sequencing performed. I think it is important to always make sure that that testing is performed. We’ll probably see many patients in the context of our careers where that’s not always standard. It should be added on before treatment decision making.

Sameer A. Parikh, MBBS: I agree with that. I think at a minimum, a TP53 [tumor protein p53] mutation study should be done.

Anthony Mato, MD, MSCE: Agree, and that’s what I meant.

Sameer A. Parikh, MBBS: In all patients.

Anthony Mato, MD, MSCE: Totally agree with you. What about the tougher question of assessing prognosis based on other comorbid conditions? I’m curious whether, as a group, we lean more towards using models like assessing a SEER [Surveillance, Epidemiology, and End Results Program] score or whether or not we are more clinical gut impressionists. How do we do that in practice? Because certainly the clinical trials tell us that we should be calculating a SEER score and if it’s greater than or equal to 6, we do this in practice when we’re sitting around with calculators calculating a score and then making a decision. You can tell by my sarcasm that I’m not, so I’m curious what others are doing.

Shuo Ma, MD, PhD: I think the Germans have done a great job in using their standardized way to look at the patient’s comorbid conditions. So they’re using the SEER score, which is cumulative in this rating scale which they are looking at different systems. I think it’s 13 different systems.

Anthony Mato, MD, MSCE: I don’t remember but it’s a lot of systems.

Shuo Ma, MD, PhD: Then for the severity of each system’s disease, you can rate from 0 to 4 and then you add all the points together, so the highest point would be 56 points. For clinical trials, I think it’s important to use a standard that everybody can follow. In fact, all of the German clinical trials, large, randomized, frontline CLL [chronic lymphocytic leukemia] clinical trials have used the SEER score. For example, the CLL11 study used a SEER score of greater than 6 as defining a patient who has significant comorbid conditions. In real life practice, I think it’s pretty difficult to look at that. Most of us, I believe, are using more of our clinical judgment.

Sameer A. Parikh, MBBS: I agree, I think the SEER score is generally reserved for patients who get on a clinical trial. On patients in routine practice, I think all of us use our “the eyeball test” as to how good a patient looks. I think certainly some objective criteria are essential. For example, we need to know what the patient’s creatinine clearance is, etcetera, to be able to make sure that we do not think about, for example, venetoclax-based treatment options in patients who have a creatinine clearance that’s low the patient can get into trouble. I think, in general practice, I don’t think the SEER scores are important to be done, but ideally it should be followed in a clinical trial.

Anthony Mato, MD, MSCE: One question I have is about age. CLL is a relative diagnosis of the elderly. The average age is 70 to 71 at diagnosis. How do you define advanced age in your CLL cohorts? Does that have any influence in your treatment decision making outside of comorbidities?

Sameer A. Parikh, MBBS: I think, age greater than 80, at least in my mind, I think of those patients a little bit differently. There were initial data from The Ohio State University where they published an initial experience of approximately 300 patients where age greater than 80 was an independent predictor of patients having the need to stop treatment or dose reduce more than the usual. That was mostly because of tolerability because of a number of side effects that those patients had. Some of our patients who are older than 80 where we think about starting ibrutinib, we might start at a slightly lower dose and then ramp up if they’re able to tolerate the lower dose of ibrutinib.

Shuo Ma, MD, PhD: I think the absolute age is important, but it’s also the physiologic age that is important, too. I guess, as we already talked about, we need to look at a patient as a whole to look at all the other medical conditions in addition to the actual age.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: Some questions about this patient to consider would be, “what is the prognosis for the patient given his molecular status and his comorbidities?” How do we evaluate those sort of independently of one another but then taking them together to make a decision for the patient?  I think the molecular status is probably the lower hanging fruit. It’s sort of easier to look at those data objectively. How would you prognosticate this patient?

Nupam A. Patel, MD: From the FISH [fluorescence in situ hybridization] perspective, we don’t have any abnormalities so that’s more of a neutral kind of prognosis. The IGHV [immunoglobulin heavy chain variable] is unmutated, and again, like we saw in previous cases, that is classically more of a poor prognosis.

Anthony Mato, MD, MSCE: Assuming we’re going to give chemotherapy.

Nupam A. Patel, MD: Exactly.

Anthony Mato, MD, MSCE: I didn’t mention whether or not this patient had next-generation sequencing performed. I think it is important to always make sure that that testing is performed. We’ll probably see many patients in the context of our careers where that’s not always standard. It should be added on before treatment decision making.

Sameer A. Parikh, MBBS: I agree with that. I think at a minimum, a TP53 [tumor protein p53] mutation study should be done.

Anthony Mato, MD, MSCE: Agree, and that’s what I meant.

Sameer A. Parikh, MBBS: In all patients.

Anthony Mato, MD, MSCE: Totally agree with you. What about the tougher question of assessing prognosis based on other comorbid conditions? I’m curious whether, as a group, we lean more towards using models like assessing a SEER [Surveillance, Epidemiology, and End Results Program] score or whether or not we are more clinical gut impressionists. How do we do that in practice? Because certainly the clinical trials tell us that we should be calculating a SEER score and if it’s greater than or equal to 6, we do this in practice when we’re sitting around with calculators calculating a score and then making a decision. You can tell by my sarcasm that I’m not, so I’m curious what others are doing.

Shuo Ma, MD, PhD: I think the Germans have done a great job in using their standardized way to look at the patient’s comorbid conditions. So they’re using the SEER score, which is cumulative in this rating scale which they are looking at different systems. I think it’s 13 different systems.

Anthony Mato, MD, MSCE: I don’t remember but it’s a lot of systems.

Shuo Ma, MD, PhD: Then for the severity of each system’s disease, you can rate from 0 to 4 and then you add all the points together, so the highest point would be 56 points. For clinical trials, I think it’s important to use a standard that everybody can follow. In fact, all of the German clinical trials, large, randomized, frontline CLL [chronic lymphocytic leukemia] clinical trials have used the SEER score. For example, the CLL11 study used a SEER score of greater than 6 as defining a patient who has significant comorbid conditions. In real life practice, I think it’s pretty difficult to look at that. Most of us, I believe, are using more of our clinical judgment.

Sameer A. Parikh, MBBS: I agree, I think the SEER score is generally reserved for patients who get on a clinical trial. On patients in routine practice, I think all of us use our “the eyeball test” as to how good a patient looks. I think certainly some objective criteria are essential. For example, we need to know what the patient’s creatinine clearance is, etcetera, to be able to make sure that we do not think about, for example, venetoclax-based treatment options in patients who have a creatinine clearance that’s low the patient can get into trouble. I think, in general practice, I don’t think the SEER scores are important to be done, but ideally it should be followed in a clinical trial.

Anthony Mato, MD, MSCE: One question I have is about age. CLL is a relative diagnosis of the elderly. The average age is 70 to 71 at diagnosis. How do you define advanced age in your CLL cohorts? Does that have any influence in your treatment decision making outside of comorbidities?

Sameer A. Parikh, MBBS: I think, age greater than 80, at least in my mind, I think of those patients a little bit differently. There were initial data from The Ohio State University where they published an initial experience of approximately 300 patients where age greater than 80 was an independent predictor of patients having the need to stop treatment or dose reduce more than the usual. That was mostly because of tolerability because of a number of side effects that those patients had. Some of our patients who are older than 80 where we think about starting ibrutinib, we might start at a slightly lower dose and then ramp up if they’re able to tolerate the lower dose of ibrutinib.

Shuo Ma, MD, PhD: I think the absolute age is important, but it’s also the physiologic age that is important, too. I guess, as we already talked about, we need to look at a patient as a whole to look at all the other medical conditions in addition to the actual age.

Transcript edited for clarity.
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