Daratumumab for Patient with High-risk Smoldering Myeloma | Rahul Banerjee | #ASH24

Hi everyone. My name is Rahul Banerjee. I'm an assistant professor of medicine at the Fred Hutchinson Cancer Center in Seattle, Washington. I'm here at the 2024 Ash meeting, American Society of Hematology in San Diego, California. And earlier today, a very interesting study, the Aquila study, or Aquila, depending on how you pronounce study was presented and published in the New England Journal of Medicine.

And it's possibly a big deal for patients with smoldering myeloma. And so I'm just giving you my thought on it. Obviously, in real life, please talk with your physician about this if you have smoldering myeloma, because every case is different. In brief, for patients with high risk smoldering myeloma. There are different tools to risk stratify patients. There's one that's called a 20 to 20 that helps us to identify patients who are at higher risk of smoldering myeloma becoming active myeloma.

And the question really is for those patients with high risk smoldering myeloma, if you intercept their disease in advance, are you able to change the natural history of the disease? It's a really tough question because a question as well should be, should we be giving myeloma treatment to patients who are asymptomatic? And the bar for that should be pretty high, obviously.

So because if someone has higher smoldering myeloma, they have anxiety. They have some, you know, it's hard to keep getting scans and scans and bloodwork and bone marrow biopsies, but they don't have symptoms. And so should you be treating them. We don't know. There have been prior studies looking, for example, at lenalidomide at revlimid to treat these patients.

And about half of patients had a response. But as all of you know, lenalidomide had a lot of side effects, a very expensive medication that can impair stem cell collection down the line. So not many of us have used it in commercial practice. The Aquila study used a different medication. So they looked at daratumumab.

Darzalex Faspro many of you are very familiar with that in the setting of active myeloma. This was a study of three years of dara, I'm going to call Daratumumab darzalex just dara for short, dara versus active observation and high risk smoldering myeloma. They enrolled several patients with multiple myeloma. But I'll focus on the high risk smoldering myeloma population. And in brief they found that using daratumumab upfront for those patients in a randomized manner where patients randomly assigned one versus the other, the patients who got dara had much lower risk of progression to multiple myeloma, including, and this was very important to me, lower risk of progression via symptoms.

For example, you know, CRAB criteria like a bone lesion showing up, not just the m-spike rising, not just a little bit of anemia, some anemia, but mainly there were patients who, who got the daratumumab, those patients who did had lower risk of again, bone lesions coming up, lower risk of MRI showing bone lesions, lower risk of anemia as we mentioned. And so I think that's very interesting. The most interesting part of the study and a lot of unanswered questions. And I'm gonna have to go back and read the internal medicine paper more carefully, is that there was an overall survival benefit. So in that particular study the patients who were randomized to get daratumumab versus those who were assigned to active observation.

The group that got dara actually lived longer. And that is a holy grail of myeloma treatments across the board. We want our patients to live better and live longer, and here we are seeing that patients are living longer. I haven't seen the patient reported outcomes, data, but presumably patients are living better as well because, you know, they're not at risk of progression back to myeloma anymore.

And so there's a lot of unanswered questions, but a lot of excitement about this. Because if this does lead to an FDA approval of a medication like daratumumab for smoldering myeloma, then all of a sudden we’ll be able to intercept these patients, these patients who are high risk of progression to myeloma, again, not everyone was smoldering myeloma.

But these patients who are high risk, we're able to offer them something that is not as toxic, doesn't have as many side effects as lenalidomide, but actually works not just to lower the risk of myeloma, but possibly to have them live longer. So again, not yet FDA approved. And I would say talk with your doctor about this. There’s a lot of nuances in terms of what smoldering, you know, smoldering myeloma over time, sometimes that can change how high risk I view someone to be.

And again, right now, as of right now, December 2024 is not FDA approved for myeloma. But already the company has submitted an application to extend the approval for dara to smoldering myeloma. So if the FDA approves it, I suspect it'll be used in more and more patients in the years to come.