Rounds with the Investigators 2012 | Multiple Myeloma
QUESTION: I'm excited about denosumab in MM, but for now is there any recommendation for bone remineralization for patients with renal insufficiency who are not candidates for bisphosphonates?
DR CHARLES FARBER: Many patients with myeloma have renal insufficiency. For patients with renal insufficiency currently, who aren’t candidates for bisphosphonates, do you have any suggestions for managing bone health?
DR NEIL LOVE: And Jeff Wolf, I mean, specifically the question, I guess, you’re asking, denosumab?
DR FARBER: Right.
DR JEFFREY WOLF: So there was a randomized trial looking at denosumab in many different diseases. And it appeared to be beneficial in, I think, breast cancer and maybe some other solid tumors.
DR GRACY JOSHUA: Prostate and —
DR FARBER: Prostate and breast.
DR WOLF: Prostate. Just shows you, 5 years ago I was in private practice and saw everybody and everything, and once I started in academics, I just don’t know about solid tumors at all.
But anyway, the data in myeloma were not convincing enough to get an approval. I think it was the study structure itself. It needs to be redone.
DR JEFFREY ZONDER: Actually, in fact, the myeloma patients did slightly worse. There weren’t enough to reach any major statistical conclusions about myeloma patients. They just — it was underpowered.
But just numerically, the myeloma patients — I mean, not so bad that it’s not worth studying. And it is being studied. But in my own — I’d have to say a patient would have to have horrendous skeletal disease to make me want to use it outside of the setting of a study.
DR WOLF: And I just wouldn’t be so hard on zoledronic acid, because certainly 50% of our patients have renal insufficiency of myeloma, but you can adjust the dose. You can adjust the frequency. The incidence of osteonecrosis of the jaw has diminished now that we’re aware of it. I don’t feel a tremendous rush to go to a drug that’s unproven.
DR LOVE: Chuck, any thoughts yourself?
DR FARBER: Outside of denosumab and bisphosphonates, are there any other measures you would do? I mean, vitamin D?
DR WOLF: We put everybody on calcium, vitamin D. We believe that that helps ultimately with restructuring of bone. The amazing thing in myeloma that you need to know about the bone disease is that if you get these patients into a complete remission and keep them there for a number of years, their lesions improve and ultimately go away. They get better. Jeffrey is giving me the high eyebrow sign.
DR LOVE: Have you seen that, Jeffrey Zonder?
DR ZONDER: Certainly there are patients with lesions that heal or improve but usually show evidence of healing. But I — going away? I don’t have a lot of patients with skeletal lesions that resolve.
DR WOLF: Take a patient you put into CR 10 years ago and do an MRI on them now. And you have some of those, I think.
DR LOVE: Steve?
DR STEVEN HAGER: There is a head-to-head trial ongoing right now between the two. The question I would have is: After progression on zoledronic acid, bony lesions, would you switch to denosumab?
DR ZONDER: No.
DR HAGER: Because of a different mechanism of action?
DR ZONDER: No.
DR LOVE: Steve, you see a lot of breast cancer, don’t you?
DR HAGER: Yes.
DR ZONDER: Just specifically, if I had a patient who was developing new bony lesions on zoledronic acid, I do not view that as a failure of zoledronic acid. I’d view that as a failure of systemic therapy. And so I would switch their therapies, but not to denosumab. I would —
DR WOLF: I totally agree with Jeff and it’s so rare these days when we see patients failing systemically, they’re not getting more bone disease. They’re getting lymph nodes and they’re getting CNS involvement and they’re getting really bizarre relapses.
DR ZONDER: But I do have to say in terms of monitoring skeletal disease, there’s a spectrum of how patients are being followed for their bone disease. And we all have colleagues in academia who cease following skeletal surveys in patients who didn’t have bone disease at the outset and who achieve a good CR. I mean, I’ve seen patients in consultation who haven’t had a skeletal survey in 3 years. And that, to me, I think it’s actually critically important to pay attention.
I would say in my own practice, 1 to 2 times per year still, we are surprised by somebody who, by the numbers on paper, looks like they’re doing well, and they, as you said, their first sign of progression is either a soft-tissue mass somewhere or a skeletal event when you wouldn’t be expecting them to have skeletal progression. And so we — I mean, at a minimum of once a year, I get skeletal surveys on patients. But in patients who aren’t in a CR, I actually tend to get them even a bit more often than that.