Fresh Versus Cryopreserved LV20.19 CAR T-Cell Therapy for Relapsed, Refractory DLBCL and Follicular Lymphoma

IntroductionAlthough cryopreservation of commercial CAR T-cell products facilitates shipping to a local site, its impact on CAR T-cell functionality, efficacy, and viability has not been evaluated. At the Medical College of Wisconsin utilizing a point-of-care manufacturing system we generally infuse fresh (non-cryopreserved) CAR T-cells when clinically feasible as our standard of care process with LV20.19 CAR T-cell therapy in an ongoing clinical trial. To better understand the impact of cryopreservation, we added a new arm where all patients’ CAR products were mandated to be cryopreserved. We now report clinical outcomes of LV20.19 CAR T-cells given fresh versus post-cryopreservation in patients with R/R DLBCL and FL.MethodsWe conducted a Phase 1/2 single center, multi-cohort clinical trial (NCT04186520) evaluating LV20.19 CAR T-cells at a fixed dose of 2.5x10e6 cells/kg for pts with R/R B-cell non-Hodgkin Lymphoma. CAR T-cells were all manufactured on-site utilizing CliniMACS Prodigy device with an 8-12 day manufacturing process depending on assigned cohort. This analysis is limited to pts with DLBCL and FL stratified by administration of a fresh CAR T-cell product administered on the day of harvest versus a CAR T-cell product administered after cryopreservation/thawing.ResultsAmong the 30 pts with DLBCL or FL who received LV20.19 CAR T-cells, 18 received a fresh while 12 received a post-cryopreserved product. All pts achieved target cell dose. There was no difference in mean age, sex, disease subtype, or prior lines of therapy (Table 1). 83% in the fresh and 75% in the cryopreserved cohort had DLBCL. The ORR was 72% for fresh versus 83% for cryopreserved products. Among responding patients (n=23), the median duration of response (DOR) was 6 months for fresh cohort and not reached in the cryopreserved cohort (Figure 1). There was no difference in the in-vivo expansion between cohorts (Figure 2A and B). In terms of toxicity, there was no difference in rates of CRS or high-grade ICANS (Table 1). The mean day to CRS was day 1 in both groups. Mean CRP and ferritin were similar in both cohorts. Pts receiving a fresh infusion generally received LV20.19 CAR T-cells 9-13 days after apheresis versus 14-24 days for those receiving a mandated cryopreserved product.ConclusionsCryopreservation of LV20.19 CAR T-cell therapy had no meaningful impact on ORR, DOR, toxicity profile, time to CRS, or in-vivo expansion. Although fresh products facilitate shorter time from apheresis to infusion, cryopreservation may allow for rapid advancement of products to multicenter trials and licensure.