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1898 Factors Predicting Long-Term Survival Following CD19 CAR T-Cell Therapy in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
CRS, survivorship, Biological, Leukemia, ALL, neurotoxicity, Diseases, CAR-Ts, Therapies, Adverse Events, Lymphoid Malignancies, Clinically relevant, Quality Improvement
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Xian Zhang, MD1,2, Junfang Yang1,2*, Wenqian Li2*, Gailing Zhang, MD.2*, Yunchao Su2*, Yanze Shi2*, Dan Song2*, Min Zhang2*, Jiujiang He2*, Li Xu2*, Jingjing Li1,2*, Xinan Lu3*, Jianqiang Li, PhD4, Xiangqun Li5*, Zhongwei Xu6*, Ziyu Li7* and Peihua Lu, MD1,2

1Beijing Lu Daopei Institute of Hematology, Beijing, China
2Hebei Yanda Lu Daopei Hospital, Langfang, China
3Immunochina Pharmaceuticals Co., Ltd., Beijing, China
4Hebei Senlang Biotechnology, Shijiazhuang, Hebei, China
5Kecellitics Biotech Co., Ltd, Beijing, China
6Bioceltech Therapeutics Co., Ltd, Beijing, China
7Tsinghua University Medical School, Beijing, China

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated promising efficacy in patients with relapsed and refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CART remains a major issue. Here, we analyzed the factors related to long-term efficacy, including overall survival (OS), leukemia-free survival (LFS) and cumulative relapse rate (CRR), following CAR-T therapy in 231 R/R B-ALL patients who achieved complete remission (CR) within one month after CAR T-cell therapy.
Patients and Methods
From April 2017 to March 2019, 254 patients with R/R B-ALL were enrolled onto one of five different clinical trials (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460) at our center and received a second generation CD19+ CAR T-cell infusion. The median infused CAR T-cell dose was 3×105/kg (range: 0.2-10×105/kg). The CAR-T/T-cell ratio and the CD19+ B lymphocyte percentage in PBLC samples from 159 of the patients were analyzed using flow cytometry on day 0, 4, 7, 11, 14, 21, and 30 following CAR T-cell infusion. We performed single continuous variate factors analysis on the influence of the CAR-T/T-cell ratio and the percentage of CD19 + B-lymphocytes in day 30 post-infusion PBLC samples on the OS, LFS, and CRR. We also analyzed the impact of patient age, BM blast count, CAR-T-cell dose, and the interval time between CAR-T-cell therapy and consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) on OS and LFS.
Among 254 patients, 231 cases achieved CR within one month after CART therapy. A total of 211 CR patients had long-term follow-up of more than 30 days with a median follow-up of 12 months (1 to 29 months). On day 30 post CAR T-cell infusion, the median CAR-T/T-cell ratio in PBLC samples was 0.51% (range: 0%-44.8%), with 59 of 169 patients (34.9%) having a CAR-T/T-cell ratio of ≥1% and 85 of 169 patients (50.3%) with a CAR-T/T-cell ratio of ≥0.5%. The median percentage of CD19+ B lymphocytes in PBLC on day 30 was 0.0% (range: 0.0%-9.4%), of which 157 of 169 patients (92.9%) had <0.5% CD19+ B-cell lymphocytes, and 137 of 169 patients (81.1%) had <0.1% CD19+ B lymphocytes on day 30.
Using a single continuous variate factors analysis, we found that increasing BM blasts and percentage of CD19+ B-lymphocytes in PBLC samples on day 30 correlated with a worse OS and LFS (Table 1). BM blasts of ≥70% were statistically significantly correlated with a worse OS and LFS when compared to BM blasts of <70% (2-year OS of 52.6% vs. 65.0%, p=0.041; 2-year LFS of 43.3% vs. 58.6%, p=0.023). Unlike the BM blast data, for the CD19+ B-lymphocytes percentage in PBLC samples on day 30, we not identify a cut-off threshold. The CAR-T/T-cell ratio in PBLC samples on day 30 had no influence on OS or LFS. Unfortunately, the CAR-T/T- cell ratio and CD19+ B-lymphocyte percentage data beyond day 30 following CAR T-cell therapy was lacking for most patients and further analysis could not be performed to understand the impact of these factors on long-term survival. In our analysis, CAR T-cell dose, the interval time between CAR T-cell infusion and allo-HSCT did not significantly correlate with OS, LFS, or relapse.
The remaining 184 patients in CR received a consolidation allo-HSCT after a median interval time of 67 days post CAR T-cell therapy (range: 30-334 days). Thirty-two of these patients (17%) relapsed with a median time to relapse of 221 days (57-490 days). The remaining 27 patients received CAR T-cell therapy only and 11 (41%) relapsed with a median time to relapse of 100 days (53-398 days). None of the four factors above had an influence on the CRR in either the bridging into allo-HSCT group or the CAR-T only group (Table 2).
Using a single continuous variate factors analysis, we found that a high BM blast count and the percentage of CD19+ B-lymphocytes in PBLC samples from R/R ALL patients on day 30 predicted a worse OS and LFS while age, the CAR-T/T-cell ratio on day 30, CAR-T cell dose, and the interval time between CAR-T cell infusion and allo-HSCT had no clear impact on long-term outcomes.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH