Hematologic Oncology Update, Issue 3, 2016 (Video Program) - Video 27Strategies for promoting Bcl-2 dependence to increase venetoclax sensitivity in patients with MM
2:05 minutes.
TRANSCRIPTION:
DR LONIAL: I think the story about Bcl-2 in myeloma is that 85% of myeloma patients or their cells are Mcl-1 dependent, which means they’re going to be intrinsically resistant to Bcl-2 inhibitors. That leaves about 15% of patients who are actually Bcl-2 dependent. And it turns out that a majority of them are 11;14 translocation patients, so patients that look more B-cell like than the average myeloma patient. They tend to express CD20. They do all the things that looks more B-cell like. So how do you take that 15% and increase it? And so one of the strategies that Dr Boise really employs is the idea of adding dexamethasone, not because dex kills myeloma but because dex pushes cells towards Bcl-2 dependence. And that’s the same thing that the other paper on glutamine and glutamine dependence also does: it pushes cells towards Bcl-2 dependence. And once you make them Bcl-2 dependent, you have a shot at them with ABT-199. DR LOVE: And have clinical responses been observed with venetoclax in myeloma? DR LONIAL: Yes, we have. And I think if you look at everybody, it’s going to be a disappointing number. But if you look at the subset that are enriched amongst the t(11;14), it’s quite striking. It’s about 40% to 45% single-agent response rate in those patients. And just as an example, there’s a patient, she’s a young lady that lives up in Pittsburgh and has seen pretty much anything you can imagine: bortezomib, carfilzomib, lenalidomide, pomalidomide, bendamustine, melphalan, transplant, cyclophosphamide, seen it all — was basically being sent for supportive care, knew somebody in Athens, Georgia that we take care of, came down and saw us, got put on ABT-199, has been in a complete remission now for 2 years with single-agent ABT-199. And it was all predicted from the laboratory studies. DR LOVE: In her? DR LONIAL: In her, yes. Yes. We took her sample and tested it. She was one of the most sensitive ones we had. |