Rounds with the Investigators 2012 | Multiple Myeloma
QUESTION: Is there any information on dose intensification of pomalidomide if pt progresses?
DR STEVEN HAGER: I have a patient who is on pomalidomide. It’s compassionate access. And she just recently progressed on 2 milligrams. And we spoke about it. She’s a physician, so she knows the literature just almost as well as I do, if not better. And so she asked: Why not go up? And there is literature, I know, from the Europeans, looking at 4 milligrams versus 2. What role is there for dose intensification?
DR NEIL LOVE: So, before you address that, I want Jeff Zonder to address the question of pomalidomide in general and this specific question. Anything else you want to say about the case? How long has she been on the 2 milligrams?
DR HAGER: About 15 months. She’s had a nice ride on it. She really is a microcosm of myeloma over the last 7, 8 years. You name it, she’s had that. She’s had osteonecrosis of the jaw. She’s had several fractures. She underwent a transplant. She’s hypogammaglobulinemic and seems to respond — she has bad infections to immunoglobulins. It seems to get her over the acute illness.
DR LOVE: Now, on the pomalidomide, did she have any side effects that you could determine?
DR HAGER: Yes, mainly cytopenias. There’s several times I’ve had to hold it just due to low blood counts and wait a week and they pop back up.
DR LOVE: So, Jeff, what about the issue of dose increase?
DR JEFFREY ZONDER: As little as we know about dose response in lenalidomide, we know even less about pomalidomide right now. I mean, I think about questions like this and with all of the drugs that we’re talking about, about going back to more intensive schedules or escalating the schedule of a drug that you’re using, is this resistant or is it resistant? Is it resistant with a capital R and progressing? That would make me less inclined to titrate dose and more inclined to move to some other class of drugs.
But it wouldn’t be — based on really the lack of data, as long as you and she have an understanding of the potential toxicities of increasing the dose, if this is something that you’re just not quite capturing control, trying to go to a higher dose to get that control is —
DR LOVE: Just to clarify, this lady had prior lenalidomide and progressed?
DR HAGER: Correct. She did.
DR LOVE: Did she ever get thalidomide?
DR HAGER: Yes — actually, yes, she did, initially, at the very beginning. So she responded to that and ultimately went to transplant.
DR LOVE: Jeff Wolf, can you just comment about pomalidomide, what it is, what we know about it, where things are heading with it?
DR CHARLES FARBER: And how do you get it?
DR LOVE: Yes. And I want to hear the story about how this happened, but let’s —
DR JEFFREY WOLF: So going in reverse, I don’t believe that any of us can get it right at the moment. Even the Mayo Clinic no longer has —
DR LOVE: But he got it. Steve got it. But … how did you get it, Steve?
DR WOLF: How long ago did you get it?
DR HAGER: It was 15 months ago.
DR WOLF: So there’s a compassionate use protocol that’s not available anymore. And then there were some trials that aren’t available anymore, and the drug has gone to the FDA for question of expedited —
DR LOVE: What do we know about it?
DR WOLF: So it appears from many Phase II and a couple of Phase IIIs, where they simply compared — or Phase II, randomized, where they compared different schedules, that in patients who are refractory to lenalidomide, perhaps 20 to 30% of patients will respond. That is, PR or better, to pomalidomide. So it appears to be a step forward in terms of the IMiDs. It’s not clear whether there’s enough overlap that — it’s a lenalidomide look-alike. But I think it probably has some spectrum that covers disease that lenalidomide doesn’t. And lenalidomide may turn out to have some disease that pomalidomide doesn’t cover, and we’ll have to work that out. Its niche when it becomes available, if it becomes available, will be for lenalidomide failures, initially.
DR LOVE: So, Jeff Zonder, when I hear stories like this — and I’ve heard other stories from investigators of people on trials who’re progressing on a lot of other stuff, including IMiDs, having clinically meaningful responses. You kind of get uncomfortable having a patient deteriorating on you, where you can’t try that. I would say the same thing for carfilzomib, which we’ll talk about in a second. Any thoughts?
DR ZONDER: I’m not sure I understood exactly what you’re —
DR LOVE: I guess it’s just kind of an uncomfortable time, to know that there’s a drug out there —
DR ZONDER: That there are drugs out there. Right.
DR WOLF: Very uncomfortable time.
DR ZONDER: I agree with you. There’s an incredible patient and physician clamor for these drugs. Pomalidomide and carfilzomib, particularly, there’s an expanded access program now for carfilzomib. And they exceeded their planned accrual to this study practically overnight. They closed it, modified the study, doubled the number of patients on it. They’re reopening it now. I mean, it’s unbelievable how patients find these drugs.