Cilta-Cel Sets New Bar in Myeloma Survival

Long-term follow-up results from the CARTITUDE-1 trial (NCT03548207) evaluating ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of relapsed/refractory multiple myeloma showed that 33% of patients remained progression-free and in remission for 5 years or longer after a single cilta-cel infusion. Data were presented by Peter M. Voorhees, MD, during the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

“There is absolutely no question that the durability of the remissions that we are seeing in this group of patients is longer than anything we have seen in a previous study,” explained Voorhees in an interview with Targeted Oncology.

In addition, the median overall survival (OS) was 60.7 months (95% CI, 41.9-not estimable), and among the 32 patients who were progression free, 12 underwent serial minimal residual disease (MRD) assessments at a single center. All of these patients were MRD-negative and had complete metabolic response via PET/CT imaging at the time of follow-up after cilta-cel without additional treatment.

According to Voorhees, a multiple myeloma specialist at Atrium Health/Levine Cancer Institute, in Charlotte, North Carolina, these findings reinforce cilta-cel's position as a new and impactful therapy in multiple myeloma.

“This is the longest median overall survival that has been reported in a clinical trial targeted at patients with heavily pretreated, relapsed/refractory disease,” he said.

In the interview, Voorhees further discussed the findings from the CARTITUDE-1 trial’s 5-year follow-up, as well as their implications for oncologists.

Targeted Oncology: What makes this 5-year follow-up from CARTITUDE-1 particularly significant?

Voorhees: I think people have been excited to see what the durability of many of these MRD-negative, complete responses would ultimately be in this group of patients. I am happy to report that out of the 97 patients on CARTITUDE-1 who are treated with cilta-cel, 33% of them are alive and free of disease progression at the 5-year mark and beyond, which is really quite remarkable given that these patients are being treated with a single infusion of cilta-cel.

How durable were the responses and remission rates seen with cilta-cel over time?

As was previously reported, the median progression-free survival at this point is approximately 35 months now. To put that in perspective, the expected median progression-free survival in a similar patient population was 4.6 months when we had less effective therapy available for these patients. At this long-term follow-up, the median duration of follow-up is approximately 5 years.

What is quite remarkable is that the median overall survival is just over 5 years in this group of patients. And that is notable because, again, going back to what we would expect in this group of patients, the median overall survival is only supposed to be approximately 1 year. So, to extend that 5 times over is really quite a remarkable achievement.

What percentage of patients remained progression-free or in remission at 5 years?
Thirty-three percent. And interestingly, there was a cohort of patients from a single institution that had serial MRD testing done on an annual basis, as well as annual PET/CT imaging. This particular center applied this practice uniformly across anyone who achieved a stringent complete response. What is remarkable is, all of these patients remain MRD-negative and in a complete metabolic response 5 years and beyond after cilta-cel therapy.

So, are these patients cured? I think it's hard to say at this point, but there's absolutely no question that the durability of the remissions that we are seeing in this group of patients is longer than anything we have seen in a previous study.

How does cilta-cel’s long-term survival data compare with other relapsed/refractory multiple myeloma therapies?

This is the longest median overall survival that's been reported in a clinical trial that has been targeted at patients with heavily pretreated, relapsed/refractory disease. The median number of lines of therapy that these patients had received was 6. And again, just based on a prospective registry study called LocoMMotion [NCT04035226], the expected median overall survival for a similar group of patients was only approximately 1 year. So, the fact that we have been able to extend median overall survival to 5 years is really quite remarkable.

What patient or disease characteristics were linked to the best long-term outcomes?

When we look at T-cell characteristics prior to leukapheresis, a higher number of T cells to neutrophils in peripheral blood was associated with long-term remission. When you look at the CAR T-cell product itself, a higher proportion of naive T cells in the CAR T cell product was associated with a more durable response. Then we will look at post cilta-cel infusion at peak expansion, a higher proportion of central memory T cells to tumor burden was associated with better long-term outcomes, more durable remissions.

And it is also important to note that, in general, at peak expansion, an increased proportion of CAR T cells to tumor burden, or what we call the effector-to-target ratio, was associated with a better long-term disease control, and I think that is important, because as we start to apply cilta-cel in earlier lines of therapy, the patients are less heavily pretreated, so we anticipate seeing a higher proportion of patients with more fit immune profiles of their CAR T cell product. We also anticipate that we can positively impact the effector-to-target ratio better, with more available therapy to control the disease prior to leukapheresis and after leukapheresis during the bridging therapy process, as CAR T cells are being manufactured. So, by optimizing T-cell fitness, by optimizing that effector-to-target ratio, we're hopeful that in earlier lines of therapy, we will see even better results than what we saw in CARTITUDE-1.

What do these results mean for the timing of CAR T in the treatment sequence?

This is a heavily pretreated patient population, but based on the characteristics of the patients that achieve these long-term remissions on this study, we think that applying CAR T-cell therapy earlier in the course of the disease makes the most sense, and you are already seeing a signal of that from the CARTITUDE-4 [NCT04181827] study with longer follow-up. That was the study that looked at cilta-cel vs standard-of-care treatment for patients who had only had 1 to 3 prior lines of therapy.

The progression-free survival curves with cilta-cel look quite favorable, relative to what we saw in CARTITUDE-1, and certainly relative to standard of care from the CARTITUDE-4 trial. And when you look at the patients with standard-risk disease treated with cilta-cel, it perhaps is a little too soon to say, but you know that progression-free survival curve for that group of patients already looks like it could be showing some signs of plateau. I think CAR T-cell therapy in general, including cilta-cel, is best suited in early relapse.

How can community oncologists prepare for managing patients eligible for cilta-cel?

First, when you are seeing a patient with relapsed multiple myeloma, think about CAR T-cell therapy, and I think it is important to communicate with your colleagues who are able to administer CAR T-cell therapy to see if it is a right fit for your patient. There's a lot of connectivity that needs to occur in order to successfully onboard patients under CAR T-cell therapy. There's treatment that needs to be applied prior to leukapheresis, which the community oncologist can manage. There's the treatment that needs to be applied during the manufacturing period that the community oncologist can provide. And then there's supportive care management, things such as monthly infusions to manage the acquired hypogammaglobulinemia that we see with these products that the community oncologist can help support as well. It is a team effort, but these therapies are incredibly effective, so we need to do our best to try and get this to more patients as we possibly can.

REFERENCE:

Voorhees PM, Martin TG, Lin Y, et al. Long-term (≥5 year) remission and survival after treatment with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2025;43(suppl 16):7507.