ASH 2024 | Smoldering myeloma highlights from ASH 2024: the AQUILA study

So it’s been an exciting year for myeloma in ASH. I say that every year and every year is truly exciting. What’s unique about this year, I would say probably the most practice-changing oral abstract in our world is actually not from active myeloma this time, is from smoldering myeloma. So the AQUILA were presented by Dr Dimopoulos earlier this morning on Monday and were just published in the New England Journal of Medicine. And in brief, that was a study of daratumumab monotherapy versus active observation in patients with smoldering myeloma. We kind of reconned it and went back and looked at patients who have high-risk smoldering myeloma by 2/20 by our modern criteria for how we consider high risk. And basically, they randomized those patients to either receive, you know, three years worth of daratumumab, subcutaneous daratumumab for three years versus observation. Unsurprisingly, they found that daratumumab lowers risk of progression. That’s pretty obvious, but the question is, is that worth it? Are you actually changing the natural history of the disease or how long patients live or how well they live? And indeed, they met that bar. They found that quality of life was better, at least preserved, in the patients that got daratumumab first of all. They found that PFS2 was better. So even after starting frontline therapy for myeloma, the patients who got it upfront still did better. and most importantly, and this is the kind of holy grail of smoldering myeloma treatment, they found a survival benefit. So they found that instead of waiting until someone gets active myeloma and giving them four drugs then, or typically three drugs in that study, a triplet regimen, and transplants, and all of this stuff when they get myeloma, if you intercept them and give them daratumumab now for three years, fixed duration therapy, we actually see an overall survival benefit. Patients are living longer and living better. So I would argue that is very practice-changing. Of course, there are two people that have not approved anywhere in the world for smoldering myeloma, but the company that makes it has already kind of submitted it for authorization. Once it’s there, I will say absolutely will be practice-changing. I will recommend this for all of my patients to kind of think about probably as a default if they have higher-smoldering myeloma, again because there was a mortality benefit. The one word of caution I would say that this particular study they did a good job of excluding patients with active myeloma. Prior studies of this per same concept of intercepting a smoldering myeloma have really been hindered by that topic of you know what if some of these patients had active myeloma and you were actually under treating them by calling a smoldering. Here everyone is required to get a PET CT or MRI or something along those those lines that rule that active myeloma. So that would be a word of caution. So when daratumumab gets approved for high-risk smoldering myeloma, before you start it, stop. And make sure your patient does not have active myeloma. You need to do a PET-CT scan, ideally a PET-CT scan and a whole body MRI, to really be sure you’re not missing that, because if they have myeloma, they should be getting myeloma induction therapy, like a quadruplet or Dara RD or something along those lines. If they do not though, daratumumab I think is very appropriate.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.