This is a great question. This study looks at the comparative safety and efficacy profile of the two FDA approved CAR T-cell products, idecabtagene vicleucel and ciltacabtagene autoleucel. This is for patients who have multiply relapsed disease and nearly all of these patients have been triple class exposed to IMiDs, PIs and CD38 monoclonal antibodies.
What was the study design?
This was a retrospective analysis, this involved about 19 centres in the United States and [??] institutions with the US Multiple Myeloma Immunotherapy Consortium. We essentially included 640 patients who were leukapheresed with the intention to receive a CAR T-cell product. Of those patients, about 55 did not proceed with an infusion, mostly due to disease progression or death. About 586 patients were infused, we had 350 with ide-cel and about 236 with cilta-cel. In addition to the primary analysis, we performed several sensitivity analyses to confirm the results. The statistical methodology utilised for the study was inverse-probability-of-treatment weighting and this is basically a type of propensity score matching to balance measured confounders between comparison arms and we do this type of methodology to preserve cohort size.
Really the main reason for the study is there isn’t a prospective randomised controlled clinical trial to look at this and we have two single arm studies that have some differences in responses and in safety and in survival. So in lieu of a randomised controlled clinical trial we did this retrospective analysis utilising inverse-probability-of-treatment weighting.
What were the results of this study?
The main results of the study showed that cilta-cel, or ciltacabtagene autoleucel, was associated with a higher likelihood of experiencing severe cytokine release syndrome, which was grade 3 or higher cytokine release syndrome, a higher likelihood of experiencing infections as well as delayed neurologic toxicities. There was a trend for increased second primary malignancies but this did not reach statistical significance. The numbers are very small so obviously this result must be interpreted with caution.
We also found that patients receiving cilta-cel were more likely to experience a better response, particularly a deeper response, and we also identified that patients receiving cilta-cel had significantly superior progression free and overall survival compared to ide-cel and this was overall and within nearly all high-risk patient subgroups.
What is the significance of these results?
As I mentioned, these results are important because we don’t have a comparison in clinical trial between these two studies. Because we saw some differences in the single arm studies it’s important to identify what patients are best for which CAR T-cell product or which patient would benefit better from [??]. We hope that this study should inform and help with clinical decision making, counsel patients and hopefully help select or guide selection of CAR T-cell products for patients proceeding with chimeric antigen receptor T-cell therapies for relapsed/refractory multiple myeloma.
