Dr Phull on Real-World vs Trial Data for CAR T-Cell Therapy in R/R Multiple Myeloma

“It’s pretty striking that there were significantly lower rates of [cytokine release syndrome (CRS)] on the real-world analysis, as opposed to in the clinical trial outcomes, especially for the cilta-cel group.”

Pooja Phull, MD, hematologist/oncologist, John Theurer Cancer Center, Hackensack University Medical Center, highlights the differences between retrospective real-world and clinical trial data for ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory multiple myeloma.

In the retrospective real-world analysis presented at the 2024 ASH Annual Meeting, patients with relapsed/refractory multiple myeloma outside of a clinical trial treated with cilta-cel (n = 57) had an overall response rate (ORR) of 86% compared with 60% in those treated with ide-cel (n = 51; P = .002). Of note, the progression-free survival (PFS) was not reached (NR) in the cilta-cel group vs 7.5 months in the ide-cel group (P < .0001); overall survival was NR in both groups (P = .12).

When comparing these data from the real-world analysis with clinical trial data, a key difference was that there response rates and outcomes were worse in the real-world data, Phull begins, noting that this reflects differences in how patients in the real-world setting receive treatment vs in trial settings where everything is much more controlled, including the patient population enrolled.

Regarding safety, Phull notes that there were significantly lower rates of CRS based on data from the real-world analysis vs clinical trial data, particularly in patients from the cilta-cel group. Within the real-world analysis, data demonstrated that safety profiles were comparable between the cilta-cel and ide-cel groups. Any-grade CRS occurred in 67.2% vs 82.2% of patients in the cilta-cel and ide-cel groups, respectively (P = .08); grade 3 or greater CRS occurred in 0% vs 2.2% of patients, respectively (P = .2).

Although there aren’t current data to confirm why CRS rates were lower in the real-world patient population, Phull emphasizes that the majority of patients still experience CRS in the real-world setting. She notes that improvements in bridging therapy could be a factor. Nevertheless, the finding of lower rates of CRS among patients in the real world is reassuring, she concludes.