-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2278 Establishment of a Dynamic Ctdna Monitoring System to Predict the Prognosis of CAR-T Cell Therapy in R/R B-NHL Patients

Program: Oral and Poster Abstracts
Session: 803. Emerging Tools, Techniques and Artificial Intelligence in Hematology: Poster I
Hematology Disease Topics & Pathways:
Minimal Residual Disease
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Linghui Zhou1*, Tao Cheng2, Yongxian HU3* and He Huang, MD4*

1The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical Colleg, Tianjin, China
3Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, HANGZHOU, China
4Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China

Introduction: The objective of this study is to establish a prediction system using circulating tumor DNA (ctDNA) to determine the effectiveness of CAR-T cell therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Furthermore, the study aims to compare the mutation characteristics between different therapeutic groups to provide guidance for the prevention and follow-up treatment of patients who fail CAR-T cell therapy.

Methods: In this part of the study, a total of 79 (192 serum samples) R/R B-NHL patients with CAR-T cell therapy were collected for ctDNA detection (187 lymphoma-related gene panel), including 62 samples before treatment (T0), 69 samples at 1 week (T1) and 62 samples at 4 weeks (T2) after reinfusion. Differences of categorical variables were tested using the chi-square test or Fisher's exact test, and differences in survival events between different groups were compared using Kaplan-Meier analysis and log-rank test.

Results: The results of Kaplan-Meier analysis showed that patients with ctDNA mutation genes >10 before CAR-T cell therapy had poorer OS (1-year OS rate: 0% vs 74.9%, 2-year OS rate: 0% vs 68%, P<0.001) and PFS (1-year PFS rate: 0% vs 52.5%, 2-year PFS rate: 0% vs 36.6%, P=0.0056). Patients with MYD88, FAT1 and BTG2 mutation before CAR-T cell therapy had poorer OS, while patients with MUC16 mutation had better OS. The CR rate in patients with TP53 mutation before CAR-T cell treatment was significantly lower than that of patients without TP53 mutation (33.3% vs 68.1%, P=0.02). However, the TP53 mutation status before treatment did not have an impact on the long-term survival of patients. All patients with TP53 mutations at 4 weeks after CAR-T cell therapy failed to achieve CR, and OS was poorer (1-year OS rate: 37.5% vs 66.4%; 2-year OS rate: 12.5% vs 56.3%, P=0.0023). For CR patients, patients with BCR mutation at 4 weeks after treatment had poorer OS (2-year OS rate: 40.9% vs 76.1%, P=0.035). At one week after CAR-T cell therapy(Figure 1), patients without mutations of CDKN2A, CBLB, APC, SPEN, KMT2D, CARD11, FOXO1 and PDGFRB, were more likely to achieve CR (76.6% vs 28.6%, P<0.001), and had better OS (1-year OS rate: 81.5% vs 38.9%, 2-year OS rate: 62.2% vs 5%, P<0.001) and PFS (1-year PFS rate: 67.2% vs 0%, P<0.001).

Conclusions: In this study, we evaluated the characteristics of gene mutation between different therapeutic groups, and a gene set was screened to predict the efficacy of CAR-T cell therapy in R/R B-NHL patients, helping clinicians accurately evaluate the efficacy and assisting in decision-making of treatment options.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH