Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Chimeric Antigen Receptor T-cell therapy in ALL: What Is Next?
Junfang Yang, et al.
The Abstract concludes: This study demonstrates technical feasibility, high efficacy and low toxicities of CD19 and CD22 CAR-T cocktail in treating patients with CD19+CD22+ relapsed/refractory B-ALL. Both patients relapsed with CD19+ leukemia suggests this cocktail treatment may reduce the risk of CD19 negative relapse. Low toxicities may relate with small number of infused CAR-T, but involvement of anti-PDL1 ScFv which is co-expressed with CD22 CAR construct cannot be excluded. Therefore, related mechanisms are currently being investigated in the lab.
Rebecca Gardner, et al.
The Abstract concludes: Preclinical testing showed superior efficacy against both CD19 and CD22 when using two separate CARs and dual transduction, compared to a single bi-specific CAR. Preliminary analysis of PLAT-05 supports feasibility of product manufacturing, and toxicity and response rates that are consistent with the reported CD19 CAR T cell experience. While the infused SCRI-CAR19x22v1 products consist of a near-uniform distribution of the 3 distinct populations, we observed selective in vivo expansion of the CD19 CAR T cell population. Further investigation is required to understand the mechanism of CD19 CAR dominance in vivo. Continued accrual of subjects is ongoing to further assess the impact of dual antigen targeting on the prevention of antigen escape and the potential to provide a more durable remission.
279 Simultaneous Targeting of CD19 and CD22: Phase I Study of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Amelia Study
Persis J Amrolia, et al.
The Abstract concludes: This interim data analysis demonstrates for the first time the feasibility and safety of simultaneous targeting of CD19 and CD22 with AUTO3. Promising efficacy was demonstrated at a dose level of 3 × 106 CAR T cells/kg, as 4/4 patients achieved MRD complete remission with no antigen negative escape at this early stage. The study continues to enrol and updated follow up and additional patient data at higher dose levels, as well as cellular kinetics and additional biomarker analysis, will be presented.
280 Efficacy and Safety of CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Cell Acute Lymphocytic Leukemia (B-cell ALL) in a Large Cohort Including Patients with Extramedullary Disease(EMD), High Leukemia Burden, BCR-ABL (+) Mutation,TP53 Mutation, and Post-Transplant Relapse
Xian Zhang, et al.
The Abstract concludes: High CR rate was achieved from CAR-T for R/R B-ALL including pts with high-risk features such as EMD, HLB, BCR-ABL+, TP53+,and relapse after allo-HSCT. CRS was manageable. CNSL is not a contraindication for CAR-T therapy. An early and high relapse rate was observed in TP53+ group. Overall, RFS was superior for pts bridging to allo-HSCT after CAR-T treatment than for those receiving CAR-T- treatment only.
Kevin A. Hay, et al.
The Abstract concludes: A high rate of MRD-neg CR was seen following CD19 CAR-T cell therapy in adult B-ALL pts and is associated with improved DFS and OS. Absence of the index clone by HTS after CAR-T cells was associated with better DFS, suggesting deeper responses are associated with improved outcomes. Stepwise multivariable modeling identifies better DFS in pts with higher pre-lymphodepletion platelet count and lower LDH, and with use of Cy/Flu lymphodepletion. After adjusting for these factors, HCT after CD19 CAR-T cells may also be associated with better DFS.
Bonnie Yates, et al.
The Abstract concludes: Sequential targeting of CD19 has anecdotally increased the possibility of CD19 negative relapses, and our data provide evidence for a similar phenomenon with sequential targeting of CD22. Most notably, CD22 expression in patients who had received prior CD22 targeted therapies was lower compared to those who did not. This may have ultimately contributed to both of the observed findings of decreased response rates and decreased durability of remission, the majority of whom relapsed with CD22 negative disease following sequential targeting. This observation contributes to the increasing fund of knowledge regarding optimization of targeted therapies.