Abstract
Background:
Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.
Methods:
A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups.
Results:
Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups.
Conclusion:
Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.
Keywords: CD19-positive B-cell ALL, Relapse/refractory, CD19 Fast-CAR-T cells, CD19 conventional CAR-T cells, allogeneic hematopoietic stem cell transplantation
Introduction
Chimeric antigen receptor T (CAR-T) cell technology, an innovative immunotherapy approach, has made groundbreaking progress in the clinical application of cluster of differentiation 19 (CD19)-positive relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with complete remission (CR) rates ranging from 67% to 93%. Several CAR-T products have been approved for clinical use worldwide.[1,2,3,4,5,6,7,8,9,10,11] However, the conventional CAR-T-cell (C-CAR-T-cell) manufacturing process, from patient-cell collection to therapeutic application, typically requires 3–4 weeks.[12] Rapid disease progression in R/R B-ALL, which is characterized by rapid proliferation of leukemic cells, can severely impact the efficacy and safety of treatment, with some patients potentially losing the opportunity to receive CAR-T-cell therapy due to disease progression. Statistics indicate that 20%–30% of B-ALL patients ultimately do not receive CAR-T-cell therapy because of rapid disease progression or manufacturing failures.[13,14] Therefore, the ability to quickly produce CAR-T cells is crucial for improving therapeutic outcomes.
The novel Fast-CAR-T (F-CAR-T) cells produced via an advanced manufacturing platform (FasTCAR) require only 24 h of production, significantly reducing the preparation time. Our center has reported preclinical findings from CD19 F-CAR-T cells, which demonstrate superior expansion capacity, enhanced tumor-killing ability, and reduced exhaustion compared with C-CAR-T cells. Additionally, the initial clinical application of CD19 F-CAR-T cells in R/R B-ALL patients resulted in a 94.4% (17/18) CR rate with minimal residual disease (MRD)-negativity.[15] However, to date, there has been no direct comparison of the clinical outcomes and long-term follow-up results between F-CAR-T-cell and C-CAR-T-cell therapies in R/R B-ALL patients. This study represents the first comparison of clinical results between 23 patients with B-ALL who received F-CAR-T cells and 21 patients who received C-CAR-T cells.
Methods
Patients and study design
We conducted a retrospective comparison of the safety and efficacy of CD19 F-CAR-T cells and CD19 C-CAR-T cells in the treatment of 44 patients with CD19-positive R/R B-ALL. Patients were recruited from the Department of Hematology at Xinqiao Hospital of Army Medical University, The Affiliated Hospital of Guizhou Medical University, Tongji Hospital, Tangdu Hospital, Zhujiang Hospital, The General Hospital of Western Theater Command, Henan Cancer Hospital, 920th Hospital of Joint Logistics Support Force, Tongren Hospital, The First Affiliated Hospital of Anhui Medical University, and The First Affiliated Hospital of Zhejiang University. From April 2015 to March 2022, 23 patients received CD19 F-CAR-T-cell therapy (F-CAR-T group), while 21 patients received C-CAR-T-cell therapy (C-CAR-T group), the latter serving as the control group. The patient characteristics were comparable between the two cohorts at the time of treatment.
The major inclusion criteria were as follows: (1) male and female patients aged 14–70 years; (2) patients diagnosed with R/R B-ALL and any one of the following conditions: (a) relapse, including two or more relapses or relapses after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with 5% blast cells; (b) refractory disease, including no CR or continuous MRD positivity after two cycles of chemotherapy with a gene mutation associated with an unfavorable prognosis or with a complex karyotype; (c) Philadelphia (Ph) chromosome-positive B-ALL with any one of the following conditions: failure to tolerate tyrosine kinase inhibitors (TKIs), progression after the first and second TKI treatments, or unsuitability for allo-HSCT; (3) patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 at study entry; (4) patients with an estimated survival time of more than three months; and (5) adequate main organ function. This study was approved by the Ethics Committee of Xinqiao Hospital (No. 2024-263-01) and was conducted according to Good Clinical Practice in China and the principles of the Declaration of Helsinki (Trial registration: ChiCTR.org.cn, ChiCTR1900023212).
Production and administration of CAR-T cells
T cells were isolated, and F-CAR-T and C-CAR-T cells were generated as previously reported.[16] F-CAR-T cells were produced with the FasTCAR platform, T cells were isolated using Dynabeads CD3/CD28 CTS (Thermo Fisher Scientific, Waltham, MA, USA).[15] The manufacturing time for F-CAR-T cells was one day, plus approximately 7 more days of quality control tests and transportation. After passing all tests, the frozen F-CAR-T cells were transported to the hospital for infusion. Quality control was performed based on the Chinese Pharmacopoeia (2015 version), and the assessments included product identification, biological efficacy, purity, cell number, general detection (e.g., sterility, endotoxin, and appearance), and negative pathogenic detection. The preinfusion immunosuppressive regimens used were as follows: fludarabine, 30 mg·m−2·day−1 for 2–4 days, and cyclophosphamide (CY), 200 mg·m−2·day−1 for 2 days. The specific dosages of the medications were adjusted based on the patient’s condition.
Allo-HSCT procedure
Allo-HSCT is recommended for patients who achieve remission with CAR-T cells. However, this treatment depends on the pre-HSCT assessment, including comorbidities and donor selection, as well as on individual reasons. All allo-HSCT patients received a myeloablative conditioning regimen as follows: Patients with HLA-identical sibling HSCT received busulfan (BU) + CY (BU 3.2 mg·kg−1·day−1 −7 days to −4 days and CY 60 mg·kg−1·day−1 −3 days to −2 days). Patients with HLA-identical unrelated HSCT received BU + CY + anti-thymocyte globulin (ATG) (BU 3.2 mg·kg−1·day−1 −7 days to −4 days, CY 60 mg·kg−1·day−1 −3 days to −2 days, and ATG 2.5 mg·kg−1·day−1 −5 days to −2 days). Patients with HLA-haploidentical relative HSCT received traditional cyclohexyl nitrosourea (CCNU) + cytarabine (Ara-C) + BU + CY + ATG (CCNU 200 mg·m−2·day−1 −9 days, Ara-C 4 g·m−2·day−1 −8 days to −7 days, BU 3.2 mg·kg−1·day−1 −6 days to −4 days, CY 1.8 g·m−2·day−1 −3 days to −2 days, and ATG 5 mg·kg−1·day−1 −5 days to −2 days.
Clinical response evaluation and toxicity grading
Hematological relapse was defined as the reappearance of blasts in the peripheral blood (PB) or as more than 5% blasts on the bone marrow (BM) smear. Morphological CR in patients with ALL was defined as the presence of less than 5% lymphoblasts in the BM without extramedullary leukemia. MRD-negative CR was defined as <0.01% lymphoblasts based on flow cytometry evaluation of the BM. Overall survival (OS) was measured from the day of intervention, and death was the end event. Leukemia-free survival (LFS) was measured from the day of intervention to the date of ALL relapse or death, whichever occurred first.
The toxicities associated with anti-CD19 C-CAR-T-cell treatment were graded according to the Common Criteria for cytokine release syndrome (CRS) following C-CAR-T-cell infusion.[17] If adverse events, such as symptoms of CRS, macrophage activation syndrome (MAS), serious infections, and/or multiple organ damage, developed, patients were actively treated and strictly monitored. Tocilizumab was prescribed to treat Grades 2–4 CRS.
Statistical analysis
The endpoint of follow-up for all the surviving patients was July 1, 2024. Descriptive statistical methods were used to evaluate patient characteristics. OS and LFS were plotted according to the Kaplan–Meier method and compared via the log-rank test. Categorical variables were assessed via Fisher’s exact test. Qualitative variables were analyzed via Student’s t-test. Unless otherwise specified, P-values were based on a two-sided hypothesis test, and P <0.05 was considered to indicate statistical significance. SPSS (version 25.0; Chicago, IL, USA) was used for the statistical analyses.
Results
Patient characteristics
In the F-CAR-T-cell therapy group, all 23 patients received CD19-28z CAR-T-cell therapy. In the C-CAR-T group, 19 patients received CD19-28z CAR-T cells, while 2 patients were treated with CD19-BBz CAR-T cells. The baseline characteristics of patients in the two groups are described in Table 1. The infusion dose in the C-CAR-T group was 10 × 105 CAR-T cells/kg (5 × 105 – 50 × 105 CAR-T cells/kg). Preclinical studies have shown that F-CAR-T cells exhibit greater expansion capabilities than C-CAR-T cells do. Consequently, we administered relatively lower doses of F-CAR-T cells: 0.5 × 105 cells/kg (n = 4), 1.0 × 105 cells/kg (n = 12), and 1.5 × 105 CAR+ T cells/kg (n = 7). The median persistence period of F-CAR-T cells in the peripheral blood was 57 days (range: 7–327 days) after infusion. The median persistence period of C-CAR-T cells in the peripheral blood was 42 days (range: 14–243 days) after infusion.
Table 1.
Baseline characteristics of CD19-positive relapsed/refractory R/R B-ALL patients in F-CAR-T group and C-CAR-Tgroup (N = 44).
| Characteristics | F-CAR-T (n = 23) | C-CAR-T (n = 21) | P values |
|---|---|---|---|
| Age (years) | 24 (14–65) | 31 (14–59) | 0.242 |
| Sex (F/M) | 11/12 | 8/13 | 0.526 |
| BCR/ABL positive | 0.272 | ||
| Yes | 5 | 2 | |
| No | 18 | 19 | |
| Prior chemotherapy cycles | 5 (3–7) | 4 (3–8) | 0.948 |
| Relapse | 14 | 17 | 0.152 |
| Refractory | 9 | 4 | |
| Blast (%) | 30 (5–97) | 34 (5–97) | 0.383 |
| 5%–50% | 15 | 14 | 0.120 |
| >50% | 8 | 7 | |
| Allo-HSCT before treatment | 3 | 7 |
Data are presented as n or median (range). allo-HSCT: Allogeneic hematopoietic stem cell transplantation; BCR/ABL: Breakpoint cluster region/Abelson; C-CAR-T cells: Conventional chimeric antigen-receptor T cells; F-CAR-T cells: Fast chimeric antigen-receptor T cells; R/R B-ALL: Relapsed/refractory B-cell acute lymphoblastic leukemia.
CR
In the F-CAR-T group, 22 of the 23 patients (95.7%) achieved morphological remission, whereas 15 of the 21 patients (71.4%) in the C-CAR-T group achieved morphological remission (P = 0.036). Additionally, 21 of the 23 patients (91.3%) in the F-CAR-T group and 14 of the 21 patients (66.7%) in the C-CAR-T group achieved MRD-negative CR (P = 0.044) [Table 2].
Table 2.
Outcomes of CD19-positive R/R B-ALL patients in F-CAR-T group and C-CAR-Tgroup (N = 44).
| Outcomes | F-CAR-T (n = 23) | C-CAR-T (n = 21) | P values |
|---|---|---|---|
| CR rate, n (%) | 22 (95.7) | 15 (71.4) | 0.036 |
| MRD negative CR rate, n (%) | 21 (91.3) | 14 (66.7) | 0.044 |
| 1-year LFS (%) | 47.8 | 38.1 | 0.384 |
| 2-year LFS (%) | 43.5 | 23.8 | 0.216 |
| 1-year OS (%) | 65.2 | 52.4 | 0.395 |
| 2-year OS (%) | 56.5 | 47.6 | 0.540 |
| CRS rate, n (%) | 21 (91.3) | 14 (66.7) | 0.044 |
| Grades 1–2 | 8 (30.4) | 11 (52.4) | |
| Grades 3–4 | 13 (56.5) | 3 (14.3) | |
| ICANS rate, n (%) | 7 (30.4) | 2 (9.5) | 0.085 |
| Grades 1–2 | 4 (17.3) | 2 (9.5) | |
| Grades 3–4 | 3 (13.0) | 0 |
CR: Complete remission; CRS: Cytokine release syndrome; C-CAR-T cells: Conventional chimeric antigen-receptor T cells; F-CAR-T cells: Fast chimeric antigen-receptor T cells; ICANS: Immune effector cell-associated neurotoxicity syndrome; LFS: Leukemia-free; MRD: Minimal residual disease; OS: Overall survival; R/R B-ALL: Relapsed/refractory B-cell acute lymphoblastic leukemia.
Survival
As of July 1, 2024, 44 patients were monitored for a period ranging from 0.94 to 78.10 months (median of 10.39 months). In the F-CAR-T group, eight patients remained in MRD-negative CR at the time of follow-up [Figure 1A]. In the C-CAR-T group, four patients remained in MRD-negative CR at follow-up [Figure 1B]. The LFS and OS rates for patients treated with F-CAR-T cells and C-CAR-T cells are shown in Figure 2. The 1-year and 2-year LFS rates for the F-CAR-T group were 47.8% (95% CI: 28.4%–66.1%) and 43.5% (95% CI: 24.9%–62.0%), respectively, whereas they were 38.1% (95% CI: 20.6%–57.0%, P = 0.384) and 23.8% (95% CI: 10.2%–43.4%, P = 0.216), respectively, for the C-CAR-T group. The 1-year and 2-year OS rates for patients in the F-CAR-T group were 65.2% (95% CI: 45.8%–84.6%) and 56.5% (95% CI: 35.7%–77.3%), respectively, whereas they were 52.4% (95% CI: 32.0%–72.8%, P = 0.395) and 47.6% (95% CI: 26.8%–68.4%, P = 0.540), respectively, for the C-CAR-T group [Table 2].
Figure 1.
Patient disease status timeline (months after infusion). (A) F-CAR-T group; (B) C-CAR-T group. CAR-T: Chimeric antigen receptor T cell; C-CAR-T: Conventional chimeric antigen-receptor T cells; CR: Complete remission; F-CAR-T: Fast chimeric antigen-receptor T cells.
Figure 2.
Comparison of LFS and OS rates in patients with CD19-positive R/R B-ALL treated with F-CAR-T cells or C-CAR-T cells or achieving CR after CAR-T cell therapy. (A) LFS of patients treated with F-CAR-T cells or C-CAR-T cells (P = 0.216); (B) OS of patients treated with F-CAR-T cells or C-CAR-T cells (P = 0.408); (C) LFS among patients who achieved CR after receiving C-CAR-T cells according to whether the patient subsequently underwent allo-HSCT. (P = 0.358); (D) OS among patients who achieved CR after receiving C-CAR-T cells according to whether the patient subsequently underwent allo-HSCT (P = 0.722). allo-HSCT: Allogeneic hematopoietic stem cell transplantation; C-CAR-T: Conventional chimeric antigen-receptor T; CR: Complete remission.; F-CAR-T: Fast chimeric antigen-receptor T; LFS: Leukemia-free survival; OS: Overall survival.
Allo-HSCT and survival
Among patients who achieved CR after CAR-T-cell therapy (n = 37), 14 patients underwent allo-HSCT. The median time from CAR-T-cell infusion to transplantation was 77 days (range: 29–500 days). Six patients received allo-HSCT from matched sibling donors, two patients received allo-HSCT from matched unrelated donors, and six patients received grafts from haploidentical donors. In the HSCT group, the 1-year and 2-year LFS rates were 57.1% (95% CI: 32.6%–76.8%) and 50.0% (95% CI: 26.8%–70.9%), respectively, whereas they were 47.8% (95% CI: 28.4%–66.1%, P = 0.506) and 34.8% (95% CI: 18.8%–54%, P = 0.356), respectively,in the non-HSCT group. The 1-year and 2-year OS rates in the HSCT group were 64.3% (95% CI: 38.8%–82.0%) and 57.1% (95% CI: 32.6%–76.8%), respectively, whereas they were 65.2% (95% CI: 45.8%–79.8%, P = 0.985) and 56.5% (95% CI: 38.2%–72.1%, P = 0.883), respectively, in the non-HSCT group [Figure 2].
In the F-CAR-T group, 41% of patients (9/22) underwent allo-HSCT after achieving CR with CAR-T-cell therapy. Among these patients, two experienced relapse and two died from transplant-related complications (severe infections). The 1-year and 2-year LFS rates in the HSCT group were 55.6% (95% CI: 26.7%–79.4%) and 55.6% (95%CI: 26.7%–79.4%), respectively, whereas they were 46.2% (95% CI: 21.6%–72.0%, P = 0.724) and 38.5% (95% CI: 16.4%–65.4%, P = 0.549), respectively, in the non-HSCT group. The 1-year and 2-year OS rates were 66.7% (95% CI: 34.0%–87.0%) and 66.7% (95% CI: 34.0%–87.0%), respectively, whereas they were 69.2% (95% CI: 41.0%–86.7%, P = 0.873) and 53.8% (95% CI: 29.1%–75.9%, P = 0.694), respectively, in the HSCT and non-HSCT groups. In the C-CAR-T group, 33.3% of patients (5/15) underwent allo-HSCT, 2 patients died from transplant-related complications (severe infections), and none relapsed. The 1-year and 2-year LFS rates were 60.0% (95% CI: 22.9%–88.4%) and 40.0% (95% CI: 11.8%–76.9%), respectively, compared with 50.0% (95% CI: 23.7%–76.3%, P = 0.491) and 30.0% (95% CI: 10.8%–60.3%, P = 0.505), and the 1-year and 2-year OS rates were 60.0% (95% CI: 22.9%–88.4%) and 40.0% (95% CI: 11.8%–76.9%), respectively, compared with 60.0% (95% CI: 31.3%–80.4%, P = 0.759) and 60.0% (95% CI: 31.3%–80.4%, P = 0.874), respectively, between the HSCT and non-HSCT groups.
Adverse events
All patients who underwent CAR-T-cell therapy exhibited hematologic toxicity that was predominantly classified as Grades 3–4. Within the F-CAR-T group, 21 patients (91.3%) experienced CRS, with 1 patient classified as Grade 1, 7 patients classified as Grade 2, 12 patients classified as Grade 3, and 1 patient as Grade 4. In addition, seven patients developed immune effector cell-associated neurotoxicity syndrome (ICANS), including two patients, two patients, and three patients with Grades 1, 2, and 3 ICANS, respectively. In the C-CAR-T group, 14 patients (66.7%) developed CRS, with 3 patients classified as Grade 1, 8 patients classified as Grade 2, 3 patients classified as Grade 3, and no patients classified as Grade 4. In addition, two patients developed ICANS, including one patient with Grade 1 ICANS and one patient with Grade 2 ICANS. All patients achieved recovery with proper management, with no deaths reported, no cases of MAS, and no other serious adverse events.
Discussion
CAR-T-cell therapy has emerged as one of the most significant milestones in cancer research in the 21st century, offering new hope for patients with R/R-ALL.[18,19,20] However, the long wait time for CAR-T-cell preparation limits its clinical application and affects the efficacy and safety of this therapy.[15] Our center has reported on a novel F-CAR-T cell, which requires only 24 h for preparation; we demonstrated a 100% success rate among 23 patients, reducing both preparation costs and medical expenses for these individuals. This clinical trial was designed because of the absence of a comparison with C-CAR-T cells, despite previous single-arm clinical studies demonstrating the efficacy and safety of F-CAR-T cells.
Our data indicate that the CR and MRD-negative rates of F-CAR-T cells were significantly greater than those of C-CAR-T cells. This finding aligns with our preclinical research, which revealed that F-CAR-T cells have stronger in vivo expansion and cytotoxic capabilities, and this allows more R/R B-ALL patients to achieve remission. Although multiple studies have shown that MRD-negative CR patients have a longer LFS and OS than MRD-positive CR patients or non-responders do,[7,14,21] our long-term follow-up data suggest that there are no statistically significant differences in LFS or OS between F-CAR-T-cell and C-CAR-T-cell therapies. However, the F-CAR-T group tended to have a greater 2-year LFS (43.5% vs. 23.8%). In addition, a greater proportion of MRD-negative CR patients in the F-CAR-T group underwent allo-HSCT, which may have influenced the observation of CAR-T persistence. The determination of long-term efficacy may require larger sample sizes and longer observation periods, which would indicate potential areas for further optimization of F-CAR-T-cell therapy.
CRS and ICANS are critical factors in evaluating the safety of CAR-T-cell therapy. This study revealed that the incidence of CRS and severe CRS (Grades 3–4) was significantly greater in the F-CAR-T group than in the C-CAR-T group, possibly due to the more rapid and robust in vivo expansion of F-CAR-T cells. However, no patients died as a direct result of CRS or ICANS, indicating that the toxicity was manageable. Earlier data suggest that the incidence of CRS and ICANS is not related to the CAR-T-cell count or disease burden,[15] suggesting areas for improvement in reducing the side effects of F-CAR-T-cell therapy in future studies.
Recent studies have indicated that early intervention with steroids and tocilizumab does not affect CAR-T-cell expansion, persistence, or function.[22] Consequently, there should be future research into the use of early or prophylactic drugs to mitigate toxicity, and preventive strategies for CRS that are specifically designed for F-CAR-T cells should be developed. Some studies have suggested that severe neurotoxicity may be linked to an increase in the permeability of the blood–brain barrier, which would facilitate the entry of a greater number of CAR-T cells into the CNS.[23,24,25] We hypothesize that this could explain why the incidence of ICANS is greater with F-CAR-T-cell therapy than with C-CAR-T-cell therapy, although further in vivo and in vitro studies are necessary for confirmation. This feature may also provide a significant clinical advantage in reducing central nervous system relapse.
The need for allo-HSCT as consolidation therapy after CAR-T-cell therapy in R/R B-ALL remains uncertain.[14,26,27,28] No studies have yet randomized post-CAR-T patients into allo-HSCT or observation groups.[29] However, current studies report that approximately 50% of patients relapse after CAR-T-cell therapy; increasing evidence suggests that consolidative allo-HSCT could improve LFS/OS, particularly for high-risk ALL patients and pediatric patients.[30,31,32,33] In this study, allo-HSCT did not significantly improve LFS or OS, potentially because of the high mortality rate from transplant-related complications; 28.6% (4/14) of patients died from severe posttransplant infections, which is comparable to the reported rates of 23%–38%.[14,17,30] It is therefore imperative to balance the risk of relapse with the mortality associated with HSCT. Future research should investigate the selection of patients who are more suitable for bridging transplantation based on the factors such as age, risk stratification, and CAR-T-cell type.
In conclusion, one-day preparation of F-CAR-T cells for the treatment of R/R B-ALL patients has been demonstrated to be highly efficacious, reliable, and safe. This method substantially reduces the manufacturing time and costs, thereby reducing the overall expense and wait time associated with CAR-T-cell therapy and making this treatment more accessible to a broader range of patients. The remission rates obtained with F-CAR-T cells are superior to those obtained with C-CAR-T cells. However, long-term efficacy comparisons will necessitate larger sample sizes for further observation. The monitoring and management of complications can also be further optimized.
Funding
This work was supported by grants the National Natural Science Foundation of China (Nos. 82341201 and 82370181), the National Key R&D Program of China (Nos. 2022YFA1103300 and 2022YFA1103304), the Chongqing Science and Health Joint Medical Research Project (No. 2024QNXM025), and the Special Project for Talent Construction in Xinqiao Hospital of Army Medical University (No. 2022XKRC001).
Conflicts of interest
None.
Footnotes
Xu Tan, Jishi Wang, and Shangjun Chen contributed equally to this work.
How to cite this article: Tan X, Wang JS, Chen SJ, Liu L, Li YH, Tu SF, Yi H, Zhou J, Wang SB, Liu LG, Ge J, Hu YX, Wang XQ, Wang L, Chen G, Yao H, Zhang C, Zhang X. Novel CD19 Fast-CAR-T cells vs. CD19 conventional CAR-T cells for the treatment of relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia. Chin Med J 2025;138:2491–2497. doi: 10.1097/CM9.0000000000003479
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