Photo Credit: Nemes Laszlo
Every year is busy for myeloma at ASH—this year was busier. There was one session where there were three back-to-back to back myeloma sessions happening at the same time. I would say if I had to choose one study that probably will be the most practice changing very soon, it would be the AQUILA study. So this study observed daratumumab in high-risk smoldering myeloma versus active observation. Dr. Vimo was the last author, Dr. Thanos Dimopoulos was the first and presenting author. It showed that there was not only a progression free survival (PFS) benefit with a progression event defined as real myeloma.
There was a PFS benefit and there was also an overall survival benefit. One of the slides he showed, it was empowered to look at PROs, patient reported outcomes, but at least at week 12. It’s not FDA approved yet, and I’m not yet starting a patient with high-risk multiple myeloma on daratumumab, but our patients with high risk moldering right now, they’re kind of stuck. Some don’t want treatment, and if they don’t want treatment, there’s always a discussion to be had. Some are nervous, right? They have baseline chronic kidney disease or they have family history of myeloma or osteoporosis, something along those lines. And the standard right now for them is either an active observation, a clinical trial, which I’ve put some of these patients on, or standard care lenalidomide, which is messy.
It has a lot of side effects but daratumumab, I would argue, is much better tolerated than lenalidomide monotherapy for these patients. I would say that would probably be the biggest one that all of us were very carefully looking at. I think there were a lot of other nice ones as well.
Those of you who know me know that I love looking at the patient experience and lowering toxicities. And so, there were two nice abstracts, one by Dr. Gordon Cook and colleagues in the UK and that was a frailty adapted induction strategy. So in brief, they randomized patients getting a triplet, not a quadruplet, but a triplet among older, frail patients to either get normal ixazomib redex—a normal triplet with reactive dose adjustments. So if they had a toxicity, then you lower the lenalidomide or the dexamethasone, etc.
Or a proactive strategy where it was based on the patient’s age, fitness, etc, and you proactively chose a lower starting dose for them. It was a mortality benefit to the latter approach. Interestingly, driven not so much by frail patients, but by the non-frail patients who were a little bit less fit but not frail. And the reason this matter is unfortunate is that a lot of these trials use the maximum tolerated doses of all these regimens. A good example is MAIA. MAIA is an excellent regimen for transplant ineligible patients, but that study used lenalidomide 25 milligram. That’s a very high dose of lenalidomide for someone older and more frail. Dexamethasone was 20 milligrams in that study, but here they showed that if you proactively go lower, you might have a survival benefit. People might not find this surprising, but I think it’s absolutely practice changing.
