Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstracts 488, 975: Venetoclax as monotherapy or in combination with bortezomib/dexamethasone for RRMM
4:16 minutes.
TRANSCRIPTION:
DR MIKHAEL: I think you’re going to hear a lot more about venetoclax in myeloma in the next year, Neil. This single-agent study — in fact, I was one of the authors on that study — we looked at venetoclax in general in relapsed myeloma. And our preliminary work demonstrated that if a patient did not have a translocation 11;14, the response rate was extremely low. But if a patient has a translocation 11;14, the response rate was between 40% and 50%. And it’s not a surprise, because in the BCL-2 pathway where this drug has activity, that’s what we see reflected in patients with a translocation 11;14, because that’s the area that’s upregulated. And what was fascinating about it, of course, is that this is a very well-tolerated oral regimen. And I can tell you, I had 2 patients on this trial, Neil, who were progressing on carfilzomib/pom/dex or literally looking at either hospice or a clinical trial and are now, 2 years later, continuing to take venetoclax. So I think it’s heralding the first of our potential boutique drugs, if you will, in someone with a very defined cytogenetic abnormality of translocation 11;14, which about 15% of myeloma patients have. So I think it underscores the importance of getting those cytogenetics. But beyond the boutique story was the second trial that was presented of venetoclax plus bortezomib and even in patients who were bortezomib resistant. And again, thinking of how we think it works, at least, it’s not a surprise that there’s synergy of these 2 drugs together. So I think the venetoclax story is still to fully unfold, but I wouldn’t be surprised if in the near future we see it as an agent specifically available for patients with translocation 11;14 and in combination with bortezomib even if patients don’t have the translocation 11;14. DR LOVE: So I was working with your colleague in Minnesota, Dr Vincent Rajkumar, and he was talking about all these exciting things with venetoclax. And I asked him a question I want to ask you, because I was surprised at his answer. But let me see how you answer it, which is, are you attempting, or have you actually accessed venetoclax outside a trial setting for select patients with myeloma? DR MIKHAEL: Thankfully, we’ve had the trial open for patients who have translocation 11;14. So I’ve not personally had to do that, although I did recommend it to a community oncologist who was able to obtain it in a patient with translocation 11;14 who for logistical reasons couldn’t come for the clinical trial. And I think it’s a little bit easier, of course, because it’s already an FDA-approved drug. Obviously a drug much earlier in development would have been a challenge to obtain. But, I mean, it is striking how it can hit that sweet spot in certain patients. I have a patient who is on the ENDURANCE trial, the carfilzomib/len/dex. He was on the carfilzomib/len/dex arm and len maintenance. And he progressed. And he had translocation 11;14, so we put him on the venetoclax study. He has the deepest response he’s ever seen despite having carfilzomib and lenalidomide before. DR LOVE: Yes. That’s fascinating. Another thing I’ve been asking investigators is the issue of TLS, tumor lysis syndrome. Obviously it’s a big issue with CLL. My understanding is, it doesn’t seem to be much of an issue with myeloma. Is that the case? DR MIKHAEL: That’s absolutely the case. It’s a very minor issue. In the early days of the trial, we had high proliferative rates, very low-proliferative-rate cohorts. We admitted everybody who potentially was a high risk. At first, actually, we admitted everybody. And we would give them hydration and so on. And we essentially had next to no tumor lysis, which is understandable, considering the difference between CLL and myeloma and the sheer tumor volume. So I don’t want to completely dismiss it. We’re still very careful to ensure that our patients are well hydrated, especially for those first few cycles. But we’ve not seen adverse outcomes of tumor lysis syndrome with venetoclax. |