3 days ago
OS Data From CARTITUDE-1: A Cure for Myeloma?
CHICAGO — The anticipated release of 5-year overall survival (OS) data from the CARTITUDE-1 trial showed that the use of ciltacabtagene autoleucel (cilta-cel) in patients with relapsed or refractory multiple myeloma (RRMM) met or exceeded expectations.
'We already knew from our initial publication that 98% of patients who got cilta-cel responded to therapy and that the majority of those responses were complete responses. We also knew that the median PFS [progression-free survival] was approximately 34 months, which is unheard of in this patient population,' said study author Peter Voorhees, MD, of Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, North Carolina, during an oral abstract session at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.
'Today we are sharing that the median OS is just over 5 years, and that one third of the study population has remained progression-free following a single cilta-cel infusion with no maintenance therapy.'
These findings were simultaneously published in the Journal of Clinical Oncology .
CARTITUDE-1 is a phase 1B/2 trial in which 97 patients with four or more prior lines of treatment for RRMM received cilta-cel. Of these patients, 45 are currently alive and in long-term follow-up in the CARTinue 15-year post-infusion study. This group is further broken down among 32 patients who have remained progression-free since their infusion and 13 patients who had progressive disease and are now in post-progressive disease follow-up.
Of the progression-free patients, 12 from a single center with annual minimal residual disease (MRD) testing remain MRD-negative at year 5 or longer.
Voorhees noted that long-term remissions were not limited to patients with standard-risk disease. 'Patients with high-risk cytogenetics like del17p, t(14;16) or t(4;14) and those with extramedullary plasmacytomas were equally likely to be progression-free,' he said.
The study team also found that patients in long-term remission had more immune-fit drug products and higher effector to target ratios at peak expansion, Voorhees said.
The discussant for this study, Krina K. Patel, MD, MSc, of MD Anderson Cancer Center in Houston told attendees that the CARTITUDE-1 OS data were 'phenomenal for these hard-to-treat patients' as she reshared Voorhees' PFS slide showing a plateau extending toward 78 months.
'I do hope this plateau continues forever for these 33% of patients, to the point where we can say it's a true cure,' Patel said. 'But I don't hold my breath because most of my patients do relapse at some point.'
Patel also noted the limitation that CARTITUDE-1 is a single-arm study. 'We know there's CARTITUDE-4, so we have randomized data that shows better performance than at least a couple of our standard care options,' she said. 'But it is hard to compare historical controls.'
Following this presentation, Voorhees sat down with Medscape Medical News . The following interview has been edited for clarity.
Since FDA approval of cilta-cel was based on CARTITUDE-1, the expectation was that longer-term data would also be very good. Why are these long-term OS results from CARTITUDE-1 so important?
The median overall survival wound up being just over 5 years, when we would have expected it to be 1 year in a similar population. One third of the patients are alive and in remission, and they've been off therapy for 5 years, which is something we've never seen before. Just as importantly, we're not seeing new safety signals, and the rates of high-grade infection seem to be declining further out from treatment, which is what we would expect with immune recovery.
Is it time to start thinking of myeloma as a potentially curable disease?
I'm always very cautious when I discuss that. Possibly there may be patients who never relapse, but I am curious to see how these next 5 years play out because if the majority of these patients remain in remission 10 years out from cilta-cel infusion, then I'll be using the word 'cure' less cautiously at that time.
We do talk a lot about functional cures in multiple myeloma: For someone newly diagnosed with standard-risk disease, they will get a three or four drug induction therapy, then a transplant followed by maintenance therapy. A lot of these patients will stay in remission well beyond 10 years and they'll pass away at an older age of unrelated causes.
What do the new CARTITUDE-1 data do to the paradigm of continuous therapy?
The other thing that has made us hesitate about using the word 'cure' in myeloma is the traditional paradigm of continuous treatment. What happens to patients in remission when you stop therapy? Are they in a long-term remission because you're keeping the heat on the disease or are they cured and what you're applying to them continuously is unnecessary? What makes the cilta-cel 5-year data so compelling is that these patients got that single infusion and a third of them are still in remission 5 years later.
Your ASCO presentation included a discussion of MRD level at 10−5 vs 10−6. Why is that important here?
Currently the best that's available as far as regular clinical practice is concerned is a 10−6 but MRD negativity is often reported at 10−5. But as so many people going through CAR T-cell therapy achieve MRD negativity at 10−5, the 10−6 level of sensitivity seems to be a better way of distinguishing those patients that might be at higher risk for disease progression vs those that are not. You're going to see us transitioning more toward using MRD negativity at 10−6 for our clinical trials going forward.
What's ahead for the CARTITUDE research program?
The expectation is the earlier you use a highly effective therapy, the better it's going to perform. We have the CARTITUDE-4 study, which compares cilta-cel with standard of care in both standard-risk and high-risk disease. CARTITUDE-5 and CARTITUDE-6 are both phase 3 studies looking at the application of cilta-cel therapy for newly diagnosed myeloma patients. For CARTITUDE-5, we're looking to see if adding cilta-cel after lenalidomide, bortezomib and dexamethasone will improve outcomes for patients not eligible to receive an upfront transplant. And in CARTITUDE-6, we're looking to see if cilta-cel can be used instead of autologous stem cell transplantation as consolidation for younger, fitter patients with newly diagnosed myeloma. And if things go the way we expect them to, we may be starting to use that word cure more often.
When did it really hit you that the cilta-cel data are better than anything else that has yet happened?
We've got several patients from CARTITUDE-1 at our institution who are still in complete remission, and they've lived a normal life for years now. We have patients on the CARTITUDE-2 program who are also long-term responders, so we see this in our everyday practice more and more. If you had told me 10 years ago that this is what we would be doing, I would've thought there's no way. But here we are doing it.
This study was funded by Johson & Johnson and Legend Biotech. Voorhees disclosed having relationships with Abbvie/Genentech, Ascentage Pharma, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Indapta Therapeutics, Janssen, Kite (a Gilead company), Nektar, Pfizer, Regeneron, Sanofi, and TeneoBio.
Patel reported ties with Abbvie, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Legend Biotech, Merck, Novartis, Pfizer, Regeneron, and Takeda.
