Peter Voorhees, MD, Atrium Health Levine Cancer Institute, Charlotte, North Carolina, shares the results from a long-term follow-up of the CARTITUDE-1 trial which evaluated the efficacy of a single infusion of ciltacabtagene autoleucel (cilta-cel) for patients with heavily pretreated relapsed/refractory multiple myeloma (R/R MM).

The results of this analysis, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed ciltacabtagene autoleucel yielded durable and deep responses at 5 years following infusion in this patient population.

Dr Vorhees stated, “It is our hope that as we apply this into the earlier continuum of therapy, that we may potentially see a higher number of people cured of MM, or at the very least patients who go into complete remission for years on end and pass away many years later of unrelated causes.”

Transcript:

This is Peter Voorhees from Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine. I'm at the 2025 annual ASCO meeting where we'll be presenting the long-term results of the CARTITUDE-1 study.

As many may already know, CARTITUDE-1 was a study that evaluated the safety and efficacy of the BCMA targeted CAR T-cell therapy, ciltacabtagene autoleucel, or what I'll now refer to as cilta-cel, for patients with relapsed/refractory multiple myeloma. This is a study that enrolled patients who had triple class exposed disease. In other words, they'd been exposed to the 3 core pillars of myeloma therapy, the CD38 antibodies, the proteasome inhibitors, and the immunomodulatory drugs. They had to have received 3 or more prior lines of therapy, or if they were refractory to both an immunomodulatory drug and proteasome inhibitor, they could come on in an earlier line of therapy.

This study previously showed that the overall response rate is 98%. Most of these responses were complete responses and minimal residual disease negative responses, and we already know that the median progression-free survival from this study was just shy of 35 months. What's remarkable about that, if you look at the LocoMMotion study, which was a contemporary registry study that looked at the same patient population treated with what we had available previously, the expected median progression-free survival was 4.6 months, and the median overall survival was only expected to be 12.4 months. This median progression-free survival of nearly 35 months is unprecedented in this patient population.

At ASCO this year, we're presenting the long-term follow up from the study, and importantly, of the 97 patients that received cilta-cel as part of this study, 33% of those patients are alive and progression-free 5 years from receipt of a single infusion of cilta-cel.

Now, 1 of the centers that participated in this study had 12 patients that were in stringent complete response, and they were doing annual MRD testing on bone marrow aspirate, and they were doing annual PET CT imaging on these patients as well. Eleven out of the 12 were MRD negative at 10-6, all of them were MRD negative at 10-5, and every single 1 of those patients was in complete metabolic response with regards to PET CT. This suggests the possibility of cure in this group of patients, or at the very least, unprecedented durability of remissions, the likes of which we've never seen before. Again, going back to the LocoMMotion study, the median overall survival for this group of patients was expected to be 12.4 months. The median overall survival with long-term follow-up on this study is just over 60 months. That's nearly 5 times what we would've expected under ordinary circumstances before the availability of this particular agent.

Also, importantly, with longer follow-up, we're not seeing additional long-term safety signals. We saw no new cases of movement and neurocognitive toxicity. We saw no new cranial nerve palsies. We saw no new demyelinating neuropathies. There were 2 additional secondary primary malignancies we saw, 1 of which was an adenocarcinoma of the lung and the other of which was squamous cell carcinoma of the anus. None of these were attributed to cilta-cel. There were several higher-grade infections that were seen, none of which were ascribed to a cilta-cel and importantly, no new secondary hematologic malignancy. No new MDS, acute myeloid leukemia, no new CAR T-cell lymphomas that have been identified with a longer follow-up. Again, this really speaks to unprecedented efficacy in this patient population.

Now, what's also interesting about this study is that when you look at the correlative analysis that we did, the numbers of T-cells to neutrophils at the time of leukapheresis was predictive of these long-term responders. When you look at the product itself after manufacturing a higher number of naive T-cells in the CAR T-cell product was associated with more durable remissions. Then at the time of peak expansion of the CAR T-cells after infusion into the patients, a higher effect to target ratio was associated with more durable responses. Interestingly, we saw a higher number of T-cells with a central memory phenotype at peak expansion in the long-term responders. This memory T-cell population may be in part an explanation as to why these patients have achieved such durable remissions.

Now, as we move cilta-cel into earlier therapy, we anticipate even better T-cell fitness of the product, and we also foresee a scenario where we can better impact the effector to target ratios with more effective therapy. The CARTITUDE-4 study is a good example of this. This was the phase 3 study that looked at cilta-cel versus standard of care for patients who had had 1 to 3 prior lines of therapy, and particularly in the standard risk patients. The durability of remissions are really quite striking at this point in the study. I'll point out that the CARTITUDE-5 and the CARTITUDE-6 studies are evaluating cilt cell as part of frontline therapy in transplant ineligible and eligible patients respectively. In CARTITUDE-6, we'll look to see if cilta-cel can actually replace transplant as part of frontline therapy for that group of patients.

It is our hope, and it remains to be seen and we'll need long follow-up to establish this, but it is our hope that as we apply this into the earlier continuum of therapy, that we may potentially see a higher number of people cured of multiple myeloma, or at the very least patients who go into complete remission for years on end and pass away many years later of unrelated causes.

Source:

Vorhees P, Martin T, 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). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 7507.