Dr. Krina K. Patel of The University of MD Anderson Cancer Center discusses encouraging new data from the MAJESTIC-3 clinical trial, which studied a combination of two immunotherapies for people with multiple myeloma after their first relapse. She explains how this approach works, what makes the results so promising, and why supportive care is essential to safely manage treatment.
Dr. Patel also shares practical insights to help patients understand where this option may fit into their care journey, offering hope while emphasizing thoughtful, individualized decision-making.
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Transcript
Lisa Hatfield:
Dr. Patel, there was some really exciting news recently that was presented about the MAJESTIC-3 trial using daratumumab (Darzalex) and teclistamab (Tecvayli) together, and I believe it’s after first relapse or on the first couple relapses. Can you talk about that study a little bit more?
Dr. Krina K. Patel:
Yeah, no, it’s really exciting. Some of the best data we’ve seen, so, this was using teclistamab as a BCMA bispecific with daratumumab as an anti-CD38 antibody And, you know, the patient population was a little different than what we see in second [line]…it is after first relapse, so patients were either in second, third, or fourth, but mostly in second line of therapy.
Only 5 percent of patients had actually had anti-CD38 before, so that is a little different than what we see in our practice today, because most of my patients are getting anti-CD38s in frontline. But the idea is that teclistamab and daratumumab together not only do both kill myeloma, but the daratumumab can actually knock down some of the regulatory T cells and B cells you have, so, in our body, we have T cells that attack and kill things, and then we have something called regulatory T cells and regulatory B cells that actually help calm the immune system down.
This is how we don’t get autoimmune disease, right? They’re the police of our system to keep things calm. But sometimes, that’s what keeps us from responding to treatments like teclistamab, where we’re trying to activate the T cells. If the regulatory cells are there, they might kind of, you know, calm it down too much where it’s not working, and so the idea is that with daratumumab, you’re killing those off, so now there’s a bigger party, and you have more effect, right, from the activating T cells, or the effector T cells.
And so the data was amazing. Again, the response rates, you know, high 80s, low 90s for different subgroups, and the PFS, so the progression-free survival, median, meaning, you know, half the patients, at 3 years was still around 83 to 84 percent. So, they’re not close to being at 50 percent of patients relapsing yet, and that’s at 3 years. So the study, the treatment that other patients got if they got randomized to the other arm that they’re comparing against was daratumumab-pomalidomide-dexamethasone (Darzalex-Pomalyst-Decadron) or daratumumab-bortezomib-dexamethasone, but most, I think most patients got the daratumumab-pomalidomide (Darzalex-Pomalyst).
And so, again, compared to that, it showed a huge benefit, that the patients getting daratumumab-teclistamab did way better than daratumumab-pomalidomide-dexamethasone. Again, most of these patients had not seen daratumumab, so it’s going to be interesting to see what happens when you’ve had that already, or if you’ve had it for a long time, you know, will adding the daratumumab make a difference?
I think the biggest…the efficacy, phenomenal, again, but the other big things to really watch out for, though, will be how we apply it in the real world, and again, having a specialist to help you with this. The infection rate, so the infection rate was over 90 percent as well, and about 53 percent had grade 3 to 4 infections, meaning that they ended up in the hospital, or were getting IV antibiotics, so not just a simple cold or anything like that.
And so, everybody started getting IVIG. There were, unfortunately, deaths on the, on the study initially because of COVID, and when patients weren’t getting IVIG. When everybody started getting IVIG, patients had a lower risk of death from infections, but really the supportive care is really important with these bispecifics.
And again, I think in the future, it’s going to be interesting. You know, I told people that for my patients, we started giving this, if I can get it approved as of right now after CAR T, or after they’ve had other cell therapies. And, so far, again, it’s early, but they’re doing well, but really the…prophylaxis and the supportive care you need is really important.
So the IVIG, making sure you’re not only on, you know, anti-shingles, or varicella treatments like valacyclovir (Valtrex), but also on anti-PJP prophylaxis continuously, something like sulfamethoxazole/trimethoprim (Bactrim) or atovaquone (Mepron) or something else, but…really, all of the supportive care is just as important as the treatment to make sure you don’t get side effects. But again, a great option for folks who don’t go to CAR T, or for after CAR T.
Lisa Hatfield:
And then, was that trial, was it looking at a limited duration of daratumumab and teclistamab, or is this ongoing until progression?
Dr. Krina K. Patel:
It is continuous. So that’s one of my biggest takeaways, too, is that…in the real world, I will stop it or go to every 3 months. They did go to monthly after a while, but even monthly is still a lot in terms of your, hitting your immune system. So, I do believe that there’s other companies that are trying to do limited or the real world. We’re doing a lot of limited duration-type studies, because again, we want patients to be able to come off all of this and kind of get their immune systems back. I think the CELMoDs are going to be great to try to bring it back, but again, letting your body just rest will also help, and maybe help a little faster.
Lisa Hatfield:
Yeah, well, great. Thank you for explaining that. That’s really important information, too.