Ran Reshef, MD, MSc, Columbia University Irving Medical Center, New York, New York, presented results from a real-world analysis evaluating the impact of differing ciltacabtagene autoleucel (cilta-cel) doses on the efficacy and safety for patients with relapsed/refractory (R/R) multiple myeloma (MM) at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

The study found that lower cell doses did not reduce cytokine release syndrome or neurotoxicity among treated patients, while higher doses showed a clear trend toward longer progression-free and overall survival. 

Dr. Reshef concluded, “future clinical trials in cell therapy, if there is a broad dose that's allowed on the trial, the impact of the cell dose within that range should be a pre-specified analysis for any future trials in this field.”

Transcript:

Hello, my name is Ran Reshef. I'm the director of the Cellular Immunotherapy Program at Columbia University Irving Medical Center in New York. I'm here at ASH and I'm here to talk about data I presented yesterday about cilta-cel focusing on the dosing of this CAR-T that we've been using now for a while.

I think everyone knows that ciltacabtagene autoleucel, or the way we call it cilta-cel, commercially Carvykti, has transformed the treatment paradigm in multiple myeloma. We are now using it as early as second-line patients and there are clinical trials examining its use in even front line patients. We see truly amazing results in our patients.

There's 1 thing that's a little bit unusual about the approval of cilta-cel and that is the dosing range, and not just in oncology, but in medicine in general. We're generally used to having a single approved dose and in the case of cilta-cel, it has a target dose of 0.75 x 10⁶ viable CAR-positive T-cells per kilogram body weight of the patient, but there's an allowed range. This is how the clinical trials were designed. The FDA and EMA approval state that the range can be between half a million and a million cells per kilogram, which means that 1 patient can receive half a million cells and a different patient can receive twice as many CAR T-cells in a Carvykti product and they will be considered as if they receive the exact same treatment. 

We were concerned that that may not be completely accurate and this question of the impact of the dose on both toxicity and efficacy has not really been addressed systematically. It has been proposed that perhaps lowering the dose would remove some of the toxicity concerns because Carvykti does have a distinct toxicity profile. In order to address this question, we use data from the US Myeloma Immunotherapy Consortium, a large consortium of 15 academic centers that are presenting, I believe, 20 or more different abstracts at ASH this year.

We looked at 751 patients to address the question of the impact of cell dose on outcomes. What we've learned is that most patients receive a cell dose that's lower than the target dose of 0.75. In fact, we know that some patients are even receiving doses that are lower than half a million cells, and those are considered out-of-specs products. About 5% of the patients in the dataset received those type of doses. But there is a broad range, and we were interested specifically in looking into that.

We could not identify any specific patient or disease characteristics that impacted the dose that patients ultimately get. Although patients with a very high number of prior lines of therapy tended to be in that very low-dose range, an impact on toxicity is not something that we could identify. We saw that the rates of CRS and ICANS were fairly similar across cell dose ranges. In fact, the highest rates of CRS and nearly the highest rates of ICANS were in the lower-dose groups. Lowering the dose does not seem to impact toxicity.

In terms of efficacy, response rates were very high as expected. It's a very active product across the board with no differences in response rates. However, when we plotted progression-free survival (PFS), while we did not achieve a statistically significant result, it was a pretty clear trend favoring high doses when it comes to progression-free survival. The 12 months PFS that was demonstrated in CARTITUDE-1 or CARTITUDE-4 was truly reproduced in our real-world data only for the highest dose group and any other type of dosing strategy led to somewhat less favorable progression-free survival. The overall survival curves also did not show any statistically significant differences but were then again ordered by the dose with the highest dose, achieving the best survival and the lowest dose achieving slightly worse survival.

With that said, Carvykti performs excellent in the real-world setting, and all patients across all dose levels have achieved outstanding PFS and overall survival, but not without any impact of the cell dose and that's really the point we're trying to communicate. We can't ignore the cell dose. 

The main conclusion is that in future clinical trials in cell therapy, if there is a broad dose that's allowed on the trial, the impact of the cell dose within that range should be a pre-specified analysis for any future trials in this field. Thank you very much.

Source:

Reshef R, Jensen A, Gordillo C, et al. Association between cilta-cel dose and efficacy and toxicity outcomes for patients with Relapsed/Refractory multiple myeloma (RRMM): A real-world analysis from the US multiple myeloma immunotherapy consortium. Dec 6-9, 2025; Orlando, FL. Abstract: 134