ONCAlert | Upfront Therapy for mRCC

Case 2: Novel Therapies for AML With MRC

Targeted Oncology
Published Online:12:39 PM, Tue July 2, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

David Alan Rizzieri, MD: In the last slide, we look at another alternative beyond this combination therapy. We look at something that has newly hit the bricks here, which is venetoclax. It’s almost good for what ails you, it seems, in so many heme malignancies. This is a phase I/II study of venetoclax plus low-dose cytarabine, and the low dose in Dr Andrew Wei, MBBS, PhD’s, abstract was 20 mg daily for 10 days, I believe. Correct me if I’m wrong on that.

This was for patients with untreated AML [acute myeloid leukemia] who were older. They had a reasonable performance status and adequate organ function. You see the most common grade 3 or greater AEs [adverse events], as was expected, would have been cytopenias and febrile neutropenia. There was some evidence of tumor lysis syndrome, as we do see with this agent, though.

The table on the right is really telling. With this combination of therapy, there were CRs [complete remissions] or CRis [complete remissions with incomplete blood count recovery] in 54% of patients, which is very encouraging for this combination. The duration of a full remission was 14.8 months for those with a CR, and you can see down the line, for variations of the types of CR, somewhat less.

One of the most interesting things to me, which relates to the prior case that was presented, is the impact on patients with what we consider high-risk genetics and lower responsivity to traditional chemotherapy. We have patients in this small study with p53 mutation. They had 3 out of 10 with a remission. Patients with an IDH1/2 had a 72% remission rate, those with FLT3 had a 44% CR rate, and those with PM1, even higher, nearly 90%.

All of this relates to a median months of survival of about 10 months in all comers. Estimated 2-year survival is 27%, which is certainly higher than what we’d expect in an elderly group of patients with AML. I think this is encouraging as we see the emerging data on applying some of the new targeted therapies to such patients.

Naval G. Daver, MD: Well, thank you very much, and to summarize, I’ve heard a lot of different approaches to the Vyxeos data, or thoughts to it. What’s really interesting is that the quality of neutropenia is different with different agents. If we said to anybody 10 years ago, “I’m going to prolong your neutrophil recovery by a week,” we would all be upset and say, “This is definitely going to cause increased induction mortality.” This did prolong it a week, and it was half the induction mortality.

I think there are other factors, like you said—mucositis, gastrointestinal [GI] toxicities—that probably have an important impact that we overlook. These are good data, and I think the FDA did a very good job in getting this approved.

The other thing we heard initially when the data came out was that people said, “Well, you know, CR/CRi rate of 47% seems lower than I can get with 7+3 [cytarabine/daunorubicin].” Actually, if you go back and you look at true patients with MRC [myelodysplasia-related changes], which almost none of the older publications really separate because it was not identified, then you really do see 35% or 38%. Comparatively, the 47% or 50% CR/CRi is actually quite meaningful. I think all-in-all, very nice data. It will be very interesting to see how we can combine this with other agents, and of course, there will be dose reductions, etcetera, but we have a lot of nice options in this population.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

David Alan Rizzieri, MD: In the last slide, we look at another alternative beyond this combination therapy. We look at something that has newly hit the bricks here, which is venetoclax. It’s almost good for what ails you, it seems, in so many heme malignancies. This is a phase I/II study of venetoclax plus low-dose cytarabine, and the low dose in Dr Andrew Wei, MBBS, PhD’s, abstract was 20 mg daily for 10 days, I believe. Correct me if I’m wrong on that.

This was for patients with untreated AML [acute myeloid leukemia] who were older. They had a reasonable performance status and adequate organ function. You see the most common grade 3 or greater AEs [adverse events], as was expected, would have been cytopenias and febrile neutropenia. There was some evidence of tumor lysis syndrome, as we do see with this agent, though.

The table on the right is really telling. With this combination of therapy, there were CRs [complete remissions] or CRis [complete remissions with incomplete blood count recovery] in 54% of patients, which is very encouraging for this combination. The duration of a full remission was 14.8 months for those with a CR, and you can see down the line, for variations of the types of CR, somewhat less.

One of the most interesting things to me, which relates to the prior case that was presented, is the impact on patients with what we consider high-risk genetics and lower responsivity to traditional chemotherapy. We have patients in this small study with p53 mutation. They had 3 out of 10 with a remission. Patients with an IDH1/2 had a 72% remission rate, those with FLT3 had a 44% CR rate, and those with PM1, even higher, nearly 90%.

All of this relates to a median months of survival of about 10 months in all comers. Estimated 2-year survival is 27%, which is certainly higher than what we’d expect in an elderly group of patients with AML. I think this is encouraging as we see the emerging data on applying some of the new targeted therapies to such patients.

Naval G. Daver, MD: Well, thank you very much, and to summarize, I’ve heard a lot of different approaches to the Vyxeos data, or thoughts to it. What’s really interesting is that the quality of neutropenia is different with different agents. If we said to anybody 10 years ago, “I’m going to prolong your neutrophil recovery by a week,” we would all be upset and say, “This is definitely going to cause increased induction mortality.” This did prolong it a week, and it was half the induction mortality.

I think there are other factors, like you said—mucositis, gastrointestinal [GI] toxicities—that probably have an important impact that we overlook. These are good data, and I think the FDA did a very good job in getting this approved.

The other thing we heard initially when the data came out was that people said, “Well, you know, CR/CRi rate of 47% seems lower than I can get with 7+3 [cytarabine/daunorubicin].” Actually, if you go back and you look at true patients with MRC [myelodysplasia-related changes], which almost none of the older publications really separate because it was not identified, then you really do see 35% or 38%. Comparatively, the 47% or 50% CR/CRi is actually quite meaningful. I think all-in-all, very nice data. It will be very interesting to see how we can combine this with other agents, and of course, there will be dose reductions, etcetera, but we have a lot of nice options in this population.

Transcript edited for clarity.
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