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2345 Anti CD19/22 Cocktail CAR T-Cell Therapy Can Improve the Outcomes of Patients with TP53-Mutated Relapsed/Refractory B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 704. Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Biological, Therapies, CAR-Ts
Sunday, December 6, 2020, 7:00 AM-3:30 PM

JIA Wei, MD, PhD1*, Min Xiao2*, Zekai Mao3*, Na Wang, MD, PhD4*, Chunrui Li, MD, PhD5, Yang Cao6*, Weimin Sun3*, Yi Xiao2*, Chaojiang Gu7*, Shangkun Zhang, PhD8*, Yicheng Zhang9, Tongcun Zhang, Ph.D.7*, Jianfeng Zhou, MD, PhD6* and Liang Huang, MD6*

1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, BALTIMORE, MD
2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong Univ, Wuhan, CHN
4Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
5Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
6Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
7Wuhan University of Science and Technology, Wuhan, China
8Wuhan Bio-Raid Biotechnology CO., LTD., Wuhan, CHN
9Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

Mutations of the Tp53 gene occur in a subset of patients with refractory/relapse B-cell lymphoma and confer an exceedingly adverse prognosis. Chimeric antigen receptor-modified (CAR) T-cell immunotherapy represents a novel promising treatment and has achieved impressive anti-tumor responses in patients with refractory or relapsed B cell malignancies. Whether CAR T cell therapy can improve the outcomes of refractory/relapse B-cell lymphoma with Tp53 mutations or high-risk functional classification of Tp53 mutations has not been fully investigated yet.

In phase 2 trial, we evaluated the anti-CAR 19/22 cocktail therapy in patients with relapsed or refractory B-cell lymphoma with Tp53 mutations. The primary endpoint was the percentage of patients with an objective response (complete and partial response). The high-risk Tp53 mutations were defined as missense mutations, ‘disruptive’ mutations and the ‘high-risk group of evolutionary action (EAp53) score. The outcome impact of CAR T cell therapy on high-risk Tp53 mutations were also assessed.

Between September 2016 to January 2020, a total of 30 patients [median age,44.0 years(range: 28.0 to 61.0)] were enrolled. The primary efficacy analysis showed that 76.7 %(95%CI: 61% to 93%)patients have best objective response(Figure 1A), while 60.0 %(95%CI: 41% to 79%)patients at month three maintained the objective response(Figure 1B). At a median follow-up of 7.95 months(range: 1.13 to 42.76), the 12-months progression-free survival and overall survival rate were 43.33% and 45.33% respectively(Figure 1C-D). The therapy led to similar serious and life-threatening toxic effects with those reported with other CAR T-cell therapies. For all 30 enrolled patients, total 32 Tp53 Mutations were detected in this cohort including 23 missense, 4 splice site mutations, 4 insertions, 2 deletions and 1 nonsense mutation. Two Tp53 mutations were found in 2 patients. 21 patients were assessed with Tp53 FISH and 14 patients (66.66%) had 17p-. There is no difference on ORR,OS and PFS in patients based on three different Tp53-specific scoring systems. The ORR at three months predicts the long-term survival of this group of patients (Figure 1E-F).

CAR19/22 T-cell cocktail therapy can improve the outcome of r/r B-cell lymphoma with high-risk of functional classification of Tp53 mutation. The patients who achieved overall response at month three can greatly benefit from CAR19/22 T-cell cocktail therapy with long-term favorable outcome.

Trial registration: ChiCTR-OPN-16008526.

Key words B cell lymphoma; CAR T-cell therapy; Tp53 mutation;outcome

Disclosures: No relevant conflicts of interest to declare.

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