EBMT 2024 | Cilta-cel as a potential new SoC for R/R multiple myeloma: insights from the CARTITUDE-4 trial

The CARTITUDE-4 study is a Phase III randomized studY where patients with relapsed/refractory myeloma, 1 to 3 prior lines of therapy, and lenalidomide refractory myeloma were enrolled. And actually 419 patients were enrolled in the study and were randomized to receive either standard of care treatment until progression, consisting of, at physician’s discretion, a combination of daratumumab, pomalidomide and dexamethasone or pomalidomide, bortezomib and dexamethasone, or the experimental arm, which consisted of at least one bridging cycle above the two options DPD and PBD, then lymphodepletion and a single infusion of cilta-cel, followed by observation only. The primary endpoint of this study was the progression-free survival, which was met. Patients in the cilta-cel arm had a lower risk of progression or death, and this was already published last year in 2023, in the New England Journal of Medicine. And among key secondary endpoints, also patient reported outcomes that we presented at the last EBMT with a median follow up of 15.9 months.

Among the PRO, we evaluated several domains, through the EuroQoL EORTC QLQ questionnaire C30 assessing several domains, functional domains, symptoms, and also global health status, the EuroQoL 5-Dimension 5-Level assessment, and the MySIm-Q questionnaire. So what we observed is that the global health status improved to a clinically meaningful improvement at month 12 in the cilta-cel arm, while it remains stable in the standard of care arm. We assessed several functional domains such as emotional, physical role, and social functioning. All these domains improved, all the scores pertaining to these domains improved in the cilta-cel arm. While they remain stable or slightly decline in the standard of care arm. Pain improved, pain scores improved in both arms, but improved to a greater extent in the cilta-cel arm, reaching a clinically meaningful improvement at month 12 as compared to the control arm, in which the improvement was not clinically meaningful. Fatigue worsened in the standard of care arm and instead in the cilta-cel arm, starting from month three onwards, we observed an improvement in fatigue as well. And when patients were asked to rate their self, their their health, through the visual analog score, which is a separate tool, they reported an improvement in their general health, throughout the study up to month 12, where we observed a clinically meaningful improvement as compared instead to the control arm where the same scores remained, basically stable.

So overall, we observed the improvement in global health status and improvement in the perception of their general health and improvement in several domains such as emotional, functional, social role and physical functioning, as well as in pain and fatigue for cilta-cel over the standard of care arm. While the same scores remain stable in patients treated with DPD or PBD. So altogether this results along with the already positive results in terms of responses, minimal residual disease negativity, and prolonged progression free survival, reinforce the use of cilta-cel as a potential new standard of care for patients with myeloma who are refractory to lenalidomide after at least one prior line of therapy.