ONCAlert | Upfront Therapy for mRCC

Case 2: Selecting a Targeted Therapy for AML With MRC

Targeted Oncology
Published Online:12:36 PM, Tue July 2, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Naval G. Daver, MD: Vyxeos is an induction-type therapy; it’s not low intensity. It has similar intensity to 7+3 [cytarabine/daunorubicin], maybe lower early mortality, but count recovery is long. Is the goal going to be—Usama, do you want to address this—to take him to transplant? What are the things you’re going to be looking for after 1 induction or 1 consolidation to consider transplanting this patient?

Usama Gergis, MD, MBA: Basically, this case is a transplanter’s dream. What we have is a patient who has 3 main risk factors for very poor outcome without transplant, age being number 1. For a 70-year-old, there is less than 5% survival without transplant long term due to poor cytogenetics and dissident MDS [myelodysplastic syndrome]. Without transplant, this patient is doomed even if he achieves a CR1 [first complete remission]. Meanwhile, he has good performance status, and other than the depression, no real bad comorbidities. The goal is in the hands of the leukemia doctors to put this patient in CR1 and take this patient to transplant as soon as possible. I must add that with the original cytogenetics and all the next-generation sequencing, we actually send typing on this patient. By doing the day 21 or 28 marrow, we have a stem cell graft. In today’s age, we have plenty of stem cell grafts, whether it’s umbilical cord in my institution, haploidentical, or others. Again, it’s a transplanter’s dream.

Naval G. Daver, MD: I love your optimism, because it’s glass half-full. A lot of transplanters think this is a transplanter’s nightmare because he has adverse cytogenetic TP53, so I hope all the transplanters are listening to your nice commentary that this is their dream.

Just one more question. Let’s say, hypothetically, the other big elephant in the room here to think about is HMA/VEN [hypomethylating agent/venetoclax]. This is a younger patient, whereas if this patient were 77, would this change your mind? Would age be the main thing you’re looking at, or would you say, “No, even if he’s 76 or 77, I would consider Vyxeos if he’s healthy.” What do you think, Dr Rizzieri? Is age the big thing, or performance status, or others?

David Alan Rizzieri, MD: I think that’s a great question, and while age is important, I don’t think these are necessarily the right cutoffs in terms of a biologic impact. There was a fairly large study published in JCO [Journal of Clinical Oncology] some years ago showing that between 45-year-old and 55-and-above patients, the biology is very different, so above that, I don’t know if there’s a real cutoff in biology there.

If we’re using age as a marker of fitness, I’m not a big fan of that. I would rather look at other measures, whether it’s SEER [the Surveillance, Epidemiology, and End Results program] or Charlson Comorbidity [Index], strictly. We certainly all have these 78-year-olds who are very fit in our eyes, who we certainly feel comfortable approaching with stem cell transplant. Having said that, have we successfully transplanted an 80-year-old patient? Sure. Is that our goal? No. There are so many other comorbidities that eventually catch up with those patients, probably not always related to transplant, that the delta of improvement there is really minimal. I think that’s where you have a long conversation about the goals of care with such patients and really try to delve into what the expected benefit is going to be.

Naval G. Daver, MD: I agree with that. It’s not an absolute, it’s a continuum, but as you get older, probably, you’re moving more and more away from intensive [chemotherapy], of course with exceptions.

Transcript edited for clarity.

 


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Naval G. Daver, MD: Vyxeos is an induction-type therapy; it’s not low intensity. It has similar intensity to 7+3 [cytarabine/daunorubicin], maybe lower early mortality, but count recovery is long. Is the goal going to be—Usama, do you want to address this—to take him to transplant? What are the things you’re going to be looking for after 1 induction or 1 consolidation to consider transplanting this patient?

Usama Gergis, MD, MBA: Basically, this case is a transplanter’s dream. What we have is a patient who has 3 main risk factors for very poor outcome without transplant, age being number 1. For a 70-year-old, there is less than 5% survival without transplant long term due to poor cytogenetics and dissident MDS [myelodysplastic syndrome]. Without transplant, this patient is doomed even if he achieves a CR1 [first complete remission]. Meanwhile, he has good performance status, and other than the depression, no real bad comorbidities. The goal is in the hands of the leukemia doctors to put this patient in CR1 and take this patient to transplant as soon as possible. I must add that with the original cytogenetics and all the next-generation sequencing, we actually send typing on this patient. By doing the day 21 or 28 marrow, we have a stem cell graft. In today’s age, we have plenty of stem cell grafts, whether it’s umbilical cord in my institution, haploidentical, or others. Again, it’s a transplanter’s dream.

Naval G. Daver, MD: I love your optimism, because it’s glass half-full. A lot of transplanters think this is a transplanter’s nightmare because he has adverse cytogenetic TP53, so I hope all the transplanters are listening to your nice commentary that this is their dream.

Just one more question. Let’s say, hypothetically, the other big elephant in the room here to think about is HMA/VEN [hypomethylating agent/venetoclax]. This is a younger patient, whereas if this patient were 77, would this change your mind? Would age be the main thing you’re looking at, or would you say, “No, even if he’s 76 or 77, I would consider Vyxeos if he’s healthy.” What do you think, Dr Rizzieri? Is age the big thing, or performance status, or others?

David Alan Rizzieri, MD: I think that’s a great question, and while age is important, I don’t think these are necessarily the right cutoffs in terms of a biologic impact. There was a fairly large study published in JCO [Journal of Clinical Oncology] some years ago showing that between 45-year-old and 55-and-above patients, the biology is very different, so above that, I don’t know if there’s a real cutoff in biology there.

If we’re using age as a marker of fitness, I’m not a big fan of that. I would rather look at other measures, whether it’s SEER [the Surveillance, Epidemiology, and End Results program] or Charlson Comorbidity [Index], strictly. We certainly all have these 78-year-olds who are very fit in our eyes, who we certainly feel comfortable approaching with stem cell transplant. Having said that, have we successfully transplanted an 80-year-old patient? Sure. Is that our goal? No. There are so many other comorbidities that eventually catch up with those patients, probably not always related to transplant, that the delta of improvement there is really minimal. I think that’s where you have a long conversation about the goals of care with such patients and really try to delve into what the expected benefit is going to be.

Naval G. Daver, MD: I agree with that. It’s not an absolute, it’s a continuum, but as you get older, probably, you’re moving more and more away from intensive [chemotherapy], of course with exceptions.

Transcript edited for clarity.

 
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