ASH 2025 | Long-term PFS benefit with cilta-cel in standard-risk patients with R/R myeloma in CARTITUDE-4

So at ASH 2025, I had the chance to present a long-term progression for survival for patients with standard cytogenetic risk included in the CARTITUDE-4 trial. So the CARTITUDE-4 trial is one of the few randomized trials that were reported with a BCMA-directed CAR-T therapy in multiple myeloma. Enrolled patients with one to three prior lines of therapy that were PI-exposed who were lenalidomide refractory and could have been daratumumab or other anti-CD38 therapy exposed in or refractory. This trial reported before, it has been updated. It shows the cell therapy gives better progression-free survival and overall survival over standard of care triplet regimens, which in this trial was DPd or PVd. 

Because of the somewhat complex plan of care that involves apheresis, bridging therapy, and administration of CAR-T, there’s a tendency to prioritize patients with high-risk disease, which is clearly a benefit from this therapy. But the emphasis here was to show the advantage, it shows the proposition of how this therapy could be beneficial even in patients with cytogenetic standard risk disease. So what we did is, I mean, the straight comparison by intention to treat has been presented before, showing great advantage for ciltacabtagene autoleucel over standard of care. And here, what we did was we focused on a cohort of patients, 60 patients, 59 patients were infused with ciltacabtagene autoleucel and had the standard risk disease. And the standard risk definition here included patients who did not have 1q deletion, 17p deletion, translocation 14;4, and translocation 14;16. And we also expanded that definition to include the patients who had this 1q gain amplification as the sole abnormality in order to mimic the population that we saw on CARTITUDE-1 with standard-risk disease since that definition in that study included those patients. 

And what we see is that patients treated with a single dose of ciltacabtagene autoleucel have a 30-month, so two and a half years, progression-free survival of 80%. If we include the definition of the ones who had 1q gain amplification, we still talk about 73%. And that is far superior to the less than 60% that you see on the CARTITUDE-1 trial with the same cytogenetic definition of standard risk. 

We had a chance to do some interesting landmark analysis, looking at the patients who arrive at the end of the first year without progression, which is the vast majority of the patients. And of those patients, 93% of those remain progression-free at one and a half year later. And those who are MRD negative, which again was more than 80%, none of those had progression in the subsequent year and a half. I think this builds into the impression we all had from the CARTITUDE-1 trial that some patients treated with cilta-cel in late-line therapy might actually never face a progression. We had that possible plateau at five years for one-third of the patients on CARTITUDE-1. And what this tells us is, not surprisingly, that proposition of potential definitive therapy might be applied to a lot more patients than one-third that we saw on CARTITUDE-1 as we use this therapy in standard risk patients in earlier lines of therapy. So it really makes a case for early use of this very effective therapy.

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