Fludarabine vs. Bendamustine Lymphodepletion Prior to CAR-T for LBCL | Alaa Ali, MD | #ASH24

My name is Ala Ali. I'm one of the physicians at the stem cell transplant and cellular immunotherapy program at MedStar Georgetown University Hospital. I'm also an assistant professor of medicine at the Department of Medicine at Georgetown University. So at this year's annual ASH meeting I will be presenting real-world experience on the comparison between bandimastine and fluderibine and cyclophosphamide for lympho depletion prior to CD19 targeting CAR T cell therapy for large B cell lymphoma. Lympho depletion is a cocktail of chemotherapy that is meant to prepare the patient's body to accept those new CAR T cells so they don't get rejected. They work via a variety of mechanisms. One of them is to reduce the patient's own lymphocytes to allow enough space for the new cells to be to engraft in the patient's body. They also reduce a lot of cytokines and prepare the tumor microenvironment also for the activity of the incoming CAR T cells. So we utilize the CIPMTR database to look at the patients who receive fluderibine and cyclophosphamide or the fluderibine-based group in comparison to the bandimastine group. And we identified 5,256 patients. About 91% or 92% of those received fluderibine-based lympho depletion and 8% received bandimastine-based lympho depletion. And when we compare the outcomes of CAR T cells, different products of CAR T cells in these two groups, the first observation was that the overall response rate is significantly lower in the bandimastine group compared to the fluderibine group. And that was confirmed in the multivariate analysis as well. However, when we compare the complete remission rates, although the complete remission rate was also significantly lower in the bandimastine group compared to the fluderibine group, when we did the multivariate analysis, there was a trend towards lower rates of complete response, but that difference was not statistically significant. In terms of survival outcomes, the lympho depletion regimen did not have any significant impact on either progression-free survival or overall survival at either 12, 6 months or 12 months. So although the bandimastines seem to have less robust response initially, the ultimate outcomes of those patients were comparable between the bandimastine-based lympho depletion and fluderibine-based lympho depletion. The main difference, though, was that the in terms of safety outcomes, so patients in the bandimastine group experienced significantly lower rates of any great CRS, severe CRS, any great icons, severe icons, as well as alongside defined as absolute neutrophil counts less than 500 or platelet counts less than 20,000 through day 30 after CAR T cell infusion. So there was a significant difference in terms of safety profile between the two approaches. CRS stands for cytokine release syndrome. It's a side effect of CAR T cell therapy that manifests itself as fever most of the time, but in severe cases it can be associated with low blood pressure and low oxygen requiring patients to be in the ICU. Now thankfully the rates of severe CRS is significantly lower than the rates of any great CRS, which is fairly common with most of the CAR T cell products, but it could be a life-threatening complication of CAR T cells that require patients to be treated in intensive care units. So I think one of the main takeaway of this study is that although a fluidary-based non-photopalic is still the standard of care, bandimastine is a viable option, especially for those who are at high risk for treatment toxicities, specifically those with higher comorbidity index, so they have heart disease or lung disease or renal disease or liver disease. I think one way to mitigate those risks is to condition them with bandimastine as opposed to fluidary-based and cyclophosphamide. The other group of patients that could be at higher risk for toxicities is elderly patients, and in those patients, especially if it's associated with comorbidities, I think bandimastine is a viable option for those patients who need CAR T cell therapy.