Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 102: Venetoclax and low-dose cytarabine in patients age 65 or older with treatment-naïve AML
3:17 minutes.
TRANSCRIPTION:
DR STEENSMA: This is a study in which venetoclax was added to low-dose cytarabine for patients who are not great candidates for intensive chemotherapy. And all of these combinations with venetoclax have a similar theme. And that is that, if we could inhibit BCL-2 with venetoclax, that may push cells that wouldn’t be killed by chemotherapy alone over the edge to die and that we might see some really remarkable response rates in diseases that traditionally are quite refractory to conventional cytotoxic. And that’s really exactly what was seen in this trial. It was with low-dose cytarabine, a combination with venetoclax. The venetoclax was given at the 600-mg-a-day dose level. We don’t see the type of tumor lysis that you see in some of the lymphoid disorders and myeloid disorders, so the escalation can be a lot quicker. In this study, the escalation was a 5-day ramp-up rather than the multiweek ramp-up that we see being used by our colleagues who treat lymphoid disorders. And the overall CR, CRI, PR rate was 61% among the 61 patients that were evaluable with this particular combination. So that’s a much higher response rate than we would see with cytarabine alone, suggesting there’s real synergy. DR LOVE: Are there any situations where you have attempted to use it outside a trial setting or would do so? DR STEENSMA: I have done outside the trial setting, as have my colleagues. The big barrier is insurance, of course. It’s not an on-label indication. Insurance companies want to see data before they’ll reimburse it. That being said, if I have somebody with, say, a complex karyotype, a p53 mutation, maybe somebody with therapy-related either high-risk MDS or AML, I know that I’m going to have a reasonable response with a hypomethylating agent. Particularly, we saw that the recent New England Journal paper with 10-day decitabine. But those are not durable. And the hope is that with venetoclax, not only can we increase the CR rate, but maybe it’ll be more durable. There’s randomized trials going on. But in the meantime, in special patients like that, we are adding this off label. DR LOVE: Any speculations about why you don’t see TLS here? DR STEENSMA: I think these cells are probably less sensitive than the lymphoid cells are to it. I think that they are extremely dependent on BCL-2 for survival, malignant lymphocytes. And I think in myeloid disorders, BCL-2 also plays a role. It’s just not as critical a survival signal, and so you don’t see the very rapid, robust tumor lysis. That being said, you can still probably get an augmented response. But there’s randomized trials going on with all these different combinations to try to prove that. |