Hematologic Oncology Update, Issue 1, 2016 (Video Program)Perspective on the use of panobinostat for relapsed/refractory MM
3:31 minutes.
TRANSCRIPTION:
DR FONSECA: We are seeing a lot of clinical trials still going on with panobinostat. It’s an interesting story. Panobinostat is arguably the first truly bench-to-bedside discovery in myeloma. So there’s very elegant work done by the group of the Dana-Farber and Dr Anderson showing how this would enhance activity of proteasome inhibitors. Subsequent to that, there were Phase III clinical trials assigned, as we all like to see them, as are presented for drug approvals. The clinical trial is positive, but there’s a “but.” And that is, the toxicity has prevented the widespread use of panobinostat, in particular the GI toxicity and the thrombocytopenia, but particularly GI toxicity, namely the diarrhea. Now, the reason I think this is still exciting, because new combinations, so combinations of panobinostat, a different dose of panobinostat or panobinostat combined with carfilzomib, with IMiDs, early data is actually quite promising and with not as much toxicity. And unfortunately, the dosing that it was administered and the combination, the schedule for bortezomib, all of those things really bring the question forward: Is there a better way to use panobinostat? So as of now, it hasn’t gained that much traction early on in relapse, just because we have so many treatment options. But I would hope and envision, again, that in the near future and as these trials continue that we would have a greater role for the use of panobinostat. DR LOVE: There was some data reported at ASH looking at panobinostat with RVd. What about that and the possibility of bringing it into the up-front setting? Or do you think there’s just so much traffic with all these other agents that’s not going to happen? DR FONSECA: There’s a lot of traffic. So the bar is very high right now. So I do think this will play a role, ultimately. And when you look at it, even when you go back to the VANTAGE study looking at vorinostat, it was positive, but just the magnitude of benefit was very discrete. I think, given we have so many other options, we decided not to pursue that. And, to some degree, that has been one of the challenges with panobinostat. But I think as more data come forward with some of those new combinations, people will think more about it. I don’t think it’s going to be the prime contender for the first relapse or the second relapse, but it’s always good to have other options for patients. DR LOVE: You mentioned other agents being combined with panobinostat. And there was a data set presented with carfilzomib where, as you were referring to, there was a modification of the dose and schedule that seemed to make it more tolerable. And I’ve heard investigators say, “I think that combination could be considered in practice,” assuming you could get it paid for, carfilzomib/panobinostat. Any thoughts about that? DR FONSECA: I think it’s clearly one of the options. I personally have not used it in an off-study setting. And I probably would be waiting for those trials to come forward. But I think it’s very exciting. And again, there’s a very, very strong scientific rationale for why this would be a worthwhile intervention. But just like it is in clinical trials of course, in clinical practice you always have that now, traffic with all those drugs that have been approved. And to your point, it’s becoming a more and more challenging thing to discuss options with patients, because as we sit with a patient who’s facing the need of treatment again and we first have to put in our heads, “Okay. What are the next steps? What should I do in those patients?” And then you go through that explanation, it becomes a much longer discussion nowadays. |