Examining safety and durable disease remission in R/R B-ALL after autologous CD19-directed CAR T cells produced by novel PRIMCAR manufacture platform.

Abstract

7026 Background: CD19 chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in the r/r B-ALL. However, the life-threatening side effect and disease relapse limited its wide application. To overcome these limitations, we established a novel PrimeCAR platform (PRIMCAR) and reported the preliminary safety and effectiveness data of MC-1-50 CAR-T cells before (Shiqi Li, et al. J Clin Oncol 2022; 40 [suppl 16]. Abstract 7008). Here, we present updated data. Methods: In this Phase I /II study (NCT04271410), MC-1-50 CAR T cells were manufactured by the PRIMCAR platform, which reduces manufacture periods to about 2 days. Patients (pts) received single-dose of MC-1-50 at dose ranged 1-5×105 CAR+/kg (Level 1, 1×105 CAR+/kg; Level 2, 2×105 CAR+/kg; Level 3, 3×105 CAR+/kg; Level 4, 5×105 CAR+/kg). Pts were pre-conditioned with fludarabine (25-30 mg/m2) and cyclophosphamide (200-300 mg/m2) daily for 3 days. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Results: 19 pts with r/r B-ALL were infused. Disease characteristics and outcomes are shown in the table. No DLTs were reported. 18 pts (94.7%) experienced CRS, including 10 (52.6%) at grade 1, 7 (36.8%) at grade 2, 1 (5.3%) at grade 3, and no ≥ 4 CRS were observed. Three pts (15.8%) experienced ICANS, including 2 (10.5%) at grade 1, 1(5.3%) at grade 2, and no ≥ 3 ICANS occurred. All patients achieved CR/CRi (BM MRD-) in the first month. All patients received no other anti-tumor therapy until relapse was confirmed. The median DOR was not reached. 6 patients confirmed relapse, including 4 were CD19 negative and 2 were CD19 positive but with CD19 gene mutation at the time of relapse. All patients in 4 dose levels had good CAR-T expansion and exhibited long persistence features. Only 3 patients experienced the loss of CAR-T. Conclusions: Treatment of r/r B-ALL at a very low dose resulted in excellent safety profiles while exhibiting a high and durable efficacy. That makes this PRIMCAR platform potential for outpatient administration in the future. Clinical trial information: NCT04271410 . [Table: see text]