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1941 CD19 CAR-T Cells Treatment Conferred a Sustained Remission in Patients with Chemotherapy-Refractory MRD in B-ALL

Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
Leukemia, ALL, CRS, Biological, Diseases, Therapies, CAR-Ts, Adverse Events, Lymphoid Malignancies
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Wenyi Lu, MD1*, Yunxiong Wei2*, Yaqing Cao1*, Xia Xiao, MD1*, Qing Li1*, Hairong Lyu1*, Yili Jiang1*, Huan Zhang1*, Jia Wang1*, Xin Li1*, Yanyu Jiang1*, Meng Juanxia1*, Yuan Ting1*, Haibo Zhu1*, Xiaoyuan He3*, Xin Jin3*, Rui Sun1*, Tao Sui1*, Kaiqi Liu4* and Mingfeng Zhao, MD, PhD1

1Department of Hematology, Tianjin First Central Hospital, Tianjin, China
2Department of Hematology, Tianjin First Center Hospital, Tianjin, China
3School of Medicine,Nankai University,China, Tianjin, China
4State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

Background: The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor-modified T (CD19 CAR-T) cells have shown excitable response in B-ALL. Recently, some studies have shown that ALL patients with lower burden had higher CR rate and lower risk of CRS after CAR-T therapy (Park, et al, NEJM. 2018; 378(5):439-448. Lee, et al, Blood.128 (22):Abstract 218.). However, its role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T in MRD-positive B-ALL patients.

Methods: Since January 2018, a total of 14 B-ALL patients with persistent (n=8) or recurrent (n=6) MRD were enrolled in the CAR-T clinical trials (ChiCTR-ONN- 16009862 and ChiCTR1800015164). The patients were from two different clinical trials about CAR-T. If patients were treated in an MRD positive state, they would be included in this analysis. All the patients received one or more infusions of autogenous CD19 CAR-T.

Results: Median age was 37.5 (13-62) years and 7 patients were female. The median dose of infused CAR-T cells was 6.78´106cells/kg, and 5 patients received more than one infusion. After one cycle of CAR-T infusion, 12 patients achieved MRD-negative remission, leading a response rate of 85.7%. Of the subgroup of 5 Ph-positive patients who subsequently underwent transplantation, 2 patients died due to transplant-related toxic effects, whereas the other 3 patients all currently alive without leukemia. Of the subgroup of 9 Ph-negative patients, 8 patients did not undergo subsequent transplantation (Figure 1). Three patients finally suffered CD19-positive relapse and 1 patient suffered CD19-negative relapse. Importantly, 4 patients (50%) are in ongoing molecular remission without transplantation, with a duration of response averaging 22.9 months (range: 12.1-28.6 months).

The most frequent adverse events were fever and hematopoietic toxicities. Ten patients (71.4%) had grade 1 or 2 cytokine release syndrome (CRS) and no patients died of CRS. At a median follow-up time of 599.5 days (range: 172-915 days), the probability of 2-year relapse-free survival and 2-year overall survival was 61.2%±14.0% and 78.6%±11.0%, respectively.

Conclusion: In conclusion, pre-emptive CD19 CAR-T treatment is an effective and safe approach and may confer a sustained remission in B-ALL patients with chemotherapy-refractory MRD.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH