SEQUENTIAL CD19- AND CD22-DIRECTED CAR-T CELL THERAPIES IN 11 REFRACTORY OR RELAPSED B-ALL CHILDREN PATIENTS
Author(s): ,
Jing Pan
Affiliations:
Department of Hematology,Beijing Boren Hospital,Beijing,China
,
BIPENG DENG
Affiliations:
Department of immunotherapy,Beijing Boren Hospital,Beijing,China
,
ZHUOJUN LIN
Affiliations:
Department of Hematology,Beijing Boren Hospital,Beijing,China
,
WEILIANG SONG
Affiliations:
Department of Hematology,Beijing Boren Hospital,Beijing,China
,
YING YANG
Affiliations:
Department of Hematology,Beijing Boren Hospital,Beijing,China
,
Alex H. Chang
Affiliations:
Clinical Translational Research Center,Tongji University School of Medicine,Shanghai,China
CHUNRONG TONG
Affiliations:
Department of Hematology,Beijing Boren Hospital,Beijing,China
EHA Library. PAN J. Jun 15, 2019; 266830; PS1213
Dr. Jing PAN
Dr. Jing PAN
Contributions
Abstract

Abstract: PS1213

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Despite promising efficacy of CD19-directed chimeric antigen receptors (CD19 CAR) T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia (r/r B-ALL), 1-year relapse rate is still high. The furtherly optimized therapeutic strategies are needed for these patients.

Aims

To evaluate the efficacy and safety of sequential CD19- and CD22-directed CAR-T cell therapies in r/r B-ALL children who did not received CAR therapy or transplantation previously.

Methods
Between August, 2017 and January, 2018, 11 pediatric patients (pts) with r/r B-ALL were enrolled in Beijing Boren Hospital to receive sequential CD19- and CD22-directed CAR T-cell therapies. There were 5 males and the median age was 8 (5-13) years old. Seven pts were relapsed diseases (with previous regimens of 22 (7-95) months of treatment) and 4 pts were refractory minimal residual disease by flow cytometry (FCM-MRD+) (with previous regimens of 18 (3-47) months of treatment)). Extramedullary diseases (EMDs) were commonly observed in 3/7 relapsed pts including 2 with exclusive EMDs. The median marrow blast of 5.58% (rang, 0% to 93.18%) blasts by FCM. Complex chromosome aberration and high-risk gene mutations were commonly observed including TP53. All pts had CD19 and CD22 expression on blasts. Two Lentiviral vectors were constructed to carry a second-generation CAR including murine anti-CD19 or humanized anti-CD22 ScFv fused to 4-1BB co-stimulatory and CD3z signaling domains. Manufacture of CAR T cells from PBMCs commenced on day 0 of leukapheresis and was completed in 7-8 days, and both protocols of 19-CART and 22-CART manufacture were the same. The doses of CD19 CAR T cells (cycle 1) and CD22 CAR T cells (cycle 2) infused were less than 5 × 106/kg. The duration between 2 cycles were less than 6 months. The CD19 CAR T-cell and CD22 CAR T-cell expansion and cytokine releasing syndrome (CRS) were monitored after infusion. The blast in BM was evaluated on day 30 (cycle 1), and EMDs were examined by imaging tests on day 30 (cycle 1). Long term follow-up was carried out from the date of infusion of CD22 CAR T cells (cycle 2).

Results
The median dose of CD19 CAR T cells (cycle 1) infused were 10 (3.3 to 42.8) × 105/kg and CD22 CAR T cells (cycle 2) infused were 5 (0.25 to 47.4) × 105/kg (P=0.766). The median duration time between 2 cycles was 2.8 (1.3 to 5.2) m. Peak expansion of CD19 CAR T cells (10.63%, range 0.2 to 68.7% CAR T/CD3+) and CD22 CART cells (19.5%, range 0.3 to 47.9% CART/CD3+) was detected at day 10 (cycle 1) and 14 (cycle 2). All pts survived for 30 days or longer and were evaluated for response, 11 (100%) achieved CR/CRi and FCM-MRD- after cycle 1. EMDs disappeared after cycle 1(Figure 1). CRS occurred in 10/11 (90.9%) pts in cycle 1 and 6/11 (54.5%) pts in cycle 2. Grade 1 neurotoxicity occurred in 1/11 pts in cycle 1 and 2/11 pts in cycle 2. Only 1 pt had grade 3 neurotoxicity in cycle 1 and fully recovered after interventions. With a median follow-up time of 7 (2.5 to 14) months, 1 pt with TP53 mutation had relapsed on 9.5m, and 1-year DFS was 50%.

Conclusion
Our study demonstrated that sequential CAR T-cell therapies are effective and safe for r/r B-ALL children who can not be bridged to transplantation and achieved improved 1-year DFS. Future trials based on larger population and longer follow-up period are needed.

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): B cell acute lymphoblastic leukemia, Immune therapy

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