Poster Discussion 1 – Immunotherapy of cancer Poster Discussion session

1185PD - Parallel comparison of 4-1BB or CD28 co-stimulated CD19-targeted chimeric antigen receptor-T cells for B-cell non-Hodgkin lymphoma (ID 3770)

Presentation Number
1185PD
Lecture Time
17:00 - 17:00
Speakers
  • Zhitao Ying (beijing, China)
Location
Bilbao Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
16:30 - 17:30

Abstract

Background

CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin lymphoma (B-NHL). However, studies comparing the clinical outcomes of 28z CAR-T versus BBz CAR-T are lacking. Analysis of our previous double-arm clinical study of 28z CAR-T and BBz CAR-T in treatment of r/r B-ALL (18 cases for each arm) revealed that BBz CAR-T showed shorter initial response time, higher tumor-killing capacity, higher overall survival rate, longer persistence, and less severe cytokine release syndrome and neurotoxicity than 28z CAR-T. This study investigated the efficacy and toxicity of both CAR-T types in B-NHL patients.

Methods

BBz CAR-T and 28z CAR-T were prepared under identical manufacturing processes. Patients with r/r B-NHL were pre-treated with fludarabine and cyclophosphamide, and infused with 28z or BBz CAR-T. Tumor burden, CAR-T persistence and adverse events were monitored. The CAR-T that induced dose-limiting toxicity in less than one patient was further evaluated based on dose escalation.

Results

Six patients were treated at the dose of 0.75-5 × 105/kg. Both types of CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within three months. Cytokines including interleukin (IL)-6 and IL-10 were increased after CAR-T infusion. The peak levels of IL-6 and IL-10 were much higher in the 28z CAR-T cohort. Severe cytokine release syndrome (CRS), CAR-T cell related encephalopathy syndrome (CRES) (≥ grade 3), and one death occurred in the 28z CAR-T cohort, resulting in the termination of recruitment of this cohort. Six more patients received BBz CAR-T cells at a dose of 1 × 106/kg with one-month CR rate of 83% and only grade 1/2 adverse events.

Conclusions

BBz CAR-T showed similar antitumor activity, but a more favorable safety profile, compared with 28z CAR-T. This study proved the competence of BBz CAR-T in B-NHL therapy, at least under our manufacturing process.

Legal entity responsible for the study

Peking University Cancer Hospital & Institute.

Funding

Immunochina Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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