614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: CAR T Cells--Refining the Approach


Conclusion cited from the abstract: This first-in-human study of CD19t T-APCs demonstrates the ability to successfully manufacture T-APCs from stored apheresis products collected for CAR T cell production. In 11 subjects receiving at least one T-APC dose to date, there has been one T-APC infusion reaction and no other significant associated toxicity. Early evidence of efficacy demonstrated by secondary expansion of CAR T cells suggests the potential of CD19t T-APCs to enhance durable CD19 CAR T cell persistence.



Conclusion cited from the abstract: In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity.



Conclusion cited from the abstract: We noted excellent CAR T cell expansion and persistence in a ALL cohort treated with the fast off-rate CAT-41BBz CAR despite their lower BM disease at treatment compared to other studies. The kinetics documented for all evaluable patients showed a 5-fold greater CAR T cell expansion and 2-fold longer half-life than responders in published series utilising tisagenlecleucel in a similar ALL cohort (Mueller et al., Blood 2017). Patients had a favourable toxicity profile with no severe (grade 3-4) CRS and equivalent disease outcomes to the ELIANA study despite having similarly advanced disease (Maude et al., NEJM 2018292). These data suggest long lived CAR T cell persistence supports stand-alone therapy for ALL with durable responses.




Conclusion cited from the abstract: AUTO1 delivers excellent early remission rates with initial data showing 83% MRD negative CR and robust CAR expansion and persistence. Despite high tumour burden, the safety profile compares favourably to other CD19 CARs, with no cases of severe CRS and only one case of Gr3 neurotoxicity. This is consistent with experience in the paediatric cohort. Updated results will be presented.



Conclusion cited from the abstract: CVP/IO is relatively well tolerated with high response rates and low toxicity despite a heavily pre-treated group of pts. Minimal residual disease data and additional Ph-like signature data are being compiled. Randomized studies will be needed to determine differences in toxicities and response rates with the various doses. However, there is a suggestion that VOD may increase with higher doses of IO and in the setting of 2 transplants. This regimen may represent a promising strategy in the treatment of elderly pts in the newly diagnosed setting.




Conclusion cited from the abstract: corticosteroids do not compromise the treatment efficacy and kinetics of CAR-T cells, could be as a feasible and effective approach to manage CAR-T associated CRSC