Hematologic Oncology Update, Issue 1, 2016 (Video Program)Integration of the newly FDA-approved oral proteasome inhibitor ixazomib into clinical practice
3:38 minutes.
TRANSCRIPTION:
DR FONSECA: Many ways you can think about it as an oral bortezomib. And it has been shown through various clinical trials to possess that proteasome inhibitor activity. Therefore, it increases the depth of response, the ability to control the disease. In particular, in the clinical trial, the time-dependent outcomes are, of course, improved and patients do better. So what I tell people, “Whenever you’re thinking about bortezomib, you could be thinking about ixazomib.” Now, it’s currently only approved, of course, in the setting of relapsed/refractory multiple myeloma, but like everything else, it will continue to move forward. And I can see how this will become part of front-line therapy for the disease. And there are several clinical trials that are testing, of course, that hypothesis at the present time. Now, the one thing to keep in mind is, there’s no free lunch, so everything comes with its pros and its cons. And I think we are all still learning about the best way to administer ixazomib to manage some of the toxicity. And in particular, the GI toxicity is something that I think one has to become familiar with. DR FONSECA: I think it’s only a minority of patients. It’s hard to quantify again now, that in the real world. I would say probably it’s going to be less than 1 in 6 patients where this is going to be more intense. But just like everyone else, even though we used it in the context of clinical trials, there’s a preselection of patients based on them being fitter, better performance status and so forth. So I think it probably will take us about a year or two as we become more familiar with the medication. DR LOVE: One of the things, though, you mentioned, that I thought when I first heard about oral proteasome inhibitors, it seemed really logical because it’s great if you can avoid parenteral therapy for a few months. But as we’ve been seeing maintenance therapy get extended longer and longer, and now I start to hear people talking about trying to bring in a proteasome inhibitor, usually bortezomib in maintenance, particularly in higher-risk situations, it seems like — I guess I should ask first of all, are there situations right now where you think about maintenance with, for example, a proteasome inhibitor and an IMiD? And how do you think it’s going to sit in terms of oral in the maintenance setting? DR FONSECA: Oh, sure we do. And I think for the patient who has high-risk markers who has completed transplant, traditionally we’ve done something analogous to VRd for maintenance. The reason we do that is that there are several clinical trials that show that the addition of bortezomib abrogates, if not altogether in some cases eliminates the high-risk implications for t(4;14) and minus 17 in 1 particular German study. It’s important to note that there are very few studies that have looked at the impact of cytogenetics in lenalidomide-based maintenance. The CALGB study did not have that information. And the IFM study has not been fully reported or published. We do have some perspective before from thalidomide-based maintenance that suggested that thalidomide was not even neutral, perhaps even worse outcomes for patients with high-risk markers. So when we talk about risk stratification, the most important scenario right now is in the post-transplant setting and for the reasons that I mentioned about, of course, the use of a proteasome inhibitor. And now that we have an oral agent, I think that would be an ideal candidate to not have to be coming back to your clinic, back and forth. If they tolerate the drug well, of course, they can get on with their lives, and we see them for the regular monitoring and still derive the benefit of a proteasome inhibitor in the post-transplant setting. |