Al-Ola Abdallah, MD: Leyla…for this case that we saw a lot of relapses. My question here is that for the CAR [chimeric antigen receptor] T-cell therapy, I think this was used appropriately waiting for the triple refractory. CAR T was approved here after patients actually progress on daratumumab, we don’t really have a standard of care. That’s a reality. We just assume that these are the options. The daratumumab-Velcade [bortezomib]-dexamethasone was an appropriate option here, but afterwards we don’t have a real standard of care. Now, we have seen some results of the KarMMa-3 and CARTITUDE-4; would you care to tell us and share some opinion about that.

Leyla O. Shune, MD: Absolutely. KarMMa-3 made a huge splash and really made us understand the value of CAR T-cell therapy. KarMMa-3 trial is a randomized trial looking at ide-cel [idecabtagene vicleucel], which is BCMA [B-cell maturation antigen] CAR T, compared to standard of care triplet [therapy] for people who have relapsed-refractory myeloma. At the minimum, [patients were] triple-exposed, triple-refractory patients.

In that study, the response rate, the PFS [progression-free survival] with the ide-cel arm was definitely superior to our standard of care combination therapy that we would use if somebody has a progress beyond 2 to 4 lines of therapy. It made us really understand [that] moving CAR T sooner in the patient’s treatment history could really improve on their PFS, their response rate, and their CRS [cytokine release syndrome].

So, this is a very exciting time for myeloma patients because, previously, we would have to wait until the failure of 4 different lines of therapy to even consider CAR T. But now we are showing on KarMMa-3 that if you move the CAR T sooner, you have a better chance of improving the outcomes of people who have been exposed to all classes of therapy. Which is now more common, because induction therapy nowadays is actually 4 drugs, so the likelihood of being refractory to every drug after second and beyond is even higher.

Al-Ola Abdallah, MD: We can also look at the fact that in the KarMMa-3 and the CARTITUDE study, you’re comparing 1 treatment vs 3 drugs. If I have a similar PFS; certainly I’ll make that change. You’re talking about quality of life, that’s one of the things. So, we have to address that issue. If you’re treating myeloma patients and you are following these patients, you’ll see exactly how significant the CAR T-cell therapy is going to impact the quality of life. If I get the same response, then why am I’m giving 3 drugs for this patient. I don’t have to worry about like giving drug holidays for the patient or discontinuing if I’m having the same response. So, do you believe that’s a standard of care now and we can actually adapt it in the future?

Leyla O. Shune, MD: Ide-cel has been submitted to the FDA, and we’re waiting to hear about approval. At ASCO [American Society of Clinical Oncology annual meeting] late-breaking abstract, we hear about cilta-cel [ciltacabtagene autoleucel], which is another CAR T that has been used in people who have progressed beyond 1 to 3 lines, and who were lenalidomide refractory. So, I think the future of myeloma therapy will see more CAR T moving higher and sooner in the treatment journey for myeloma patients.

Al-Ola Abdallah, MD: Well, until we see that happen, we’ll still talk about the standard of care for using the ide-cel and cilta-cel after 4 lines of therapy in these patients. But before we talk about the studies for that that were approved, I think the [most common] question I receive… [Is about the] waiting list and the slot availability. I think at the beginning it was chaos. What’s our new status? What’s our recent status about the slots available to you, our institution, other institutions, for the CAR T cells?

Nausheen Ahmed, MD: Yes. So, the slot availability, as you brought up, we are coming into the more practical [way to] deliver these therapies. Although we know there’s efficacy. I can actually just talk a little bit about the efficacy before we go into access. We know ide-cel is currently being used both of these CAR Ts in 4 or greater lines of therapy. So, really, [the] relapse-refractory patients. With ide-cel, we know that there’s a progression-free survival of 8.8 to 11 months, which is very good compared to the historical standard where these patients have survival of typically less than 6 months. Cilta-cel also has very good responses where we have PFS and OS [overall survival], but recent data showing that it’s not reached. And reaching MRD [minimal residual disease]. So, we have great outcomes with both of these CARs. It’s not the best, there’s still room for improvement, but at least it’s much better than the historical standard.

So, the question when we were faced with rolling out these CARs, was that there were limited slots, especially in the beginning back in 2021. Many patients [were] waiting, but we didn’t have enough slots. I would say [there were] anywhere from 1 to 3 slots on an average in a month for these patients. We had maybe 10-plus patients every month whom we were seeing that needed the CAR T…Many centers have described their ethical dilemma in trying to select the most appropriate patients. One other thing to consider, Abdallah, when we are treating these patients, is the time to manufacture. That definitely has to be factored in. It’s anywhere from 4 to 8 weeks, and for these patients who have overall survival of less than 6 months, it’s a huge deal.

Al-Ola Abdallah, MD: Correct.

Nausheen Ahmed, MD: So, we have many patients whom we cannot select because of that. Their disease is either just exploding, the pace of the disease is too fast to get them CAR T-cell therapy. So, we’ve dealt with all of that. Now I can tell you, I think the slot issues are getting much better. I think there were other variables like manufacturing and finding the viral vector that have all been sorted out or are in the process of being sorted out. So, we should have unlimited slots.

Al-Ola Abdallah, MD: Excellent. That’s really helpful a lot for us to know about that, especially that was the biggest issue here.

Transcript edited for clarity.