Hematologic Oncology Update, Issue 1, 2016 (Video Program)Activity and tolerability of ibrutinib/palbociclib in relapsed/refractory MCL
2:29 minutes.
TRANSCRIPTION:
DR LEONARD: The drug palbociclib, which your audience is probably familiar with with breast cancer, it’s a cell-cycle inhibitor. And, obviously, mantle-cell lymphoma, cell cycle is important with cyclin D1 expression. And so having a drug that can target CDK4 and CDK6 makes a lot of sense. There are a few other cell cycle inhibitors out there, but this is the one that’s approved for breast cancer. We did a study with the Dana-Farber group a couple of years ago showing that palbociclib had single-agent activity in relapsed mantle-cell lymphoma and also that it hit the target, that we could demonstrate that Ki-67 expression and other markers of cell cycle actually went down when you gave the drug. So it was a nice translational study. We have a lot of preclinical data from Selina Chen-Kiang in our group at Cornell. And Peter Martin has led this study, where, as you know, ibrutinib has about a 70% response rate in relapsed patients, roughly a year PFS, give or take. And so the idea is that by adding palbociclib, can we improve the response rate, improve the durability? There’s a lot of preclinical data. We’ve done tumor biopsies before and after treatment and shown that we’ve changed some of the cell cycle proteins appropriately. And it’s an ongoing study, but we do seem to be seeing more CRs than you’d expect with ibrutinib alone, although obviously one would need a randomized trial to do that. But this is nice because it’s an oral agent. There’s a little more cytopenias when you add this drug to the ibrutinib. That’s one of the side effects of palbociclib that people are no doubt familiar with. But it’s a pretty manageable oral regimen, so we’ll see where it goes. DR LOVE: Of course in breast cancer, they’re combining it with hormone therapy, which usually doesn’t cause any problems. But I’ve heard the breast cancer people really comment on the neutropenia, even though it seems like they don’t see many neutropenic infections. But they’re constantly getting counts. There are a lot of dose adjustments. Is that what you’re seeing here with mantle-cell? DR LEONARD: Yes, exactly. I mean, we are using in this trial lower doses of palbociclib than you would give in mantle-cell. You can see the target’s hit with lower doses, but yes, that’s it. And you would expect that hematopoietic progenitor cells are cycling and that a cell cycle inhibitor is going to give you some cytopenias. So it’s not a huge surprise. |