Long-Term Outcomes and Adverse Events of CAR T-19 Cell Therapy in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia - a Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Background: Acute lymphoblastic leukemia (ALL) is a prevalent cancer affecting both children and adults. Despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT), many patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) fail to achieve long-term remission. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment modality. This systematic review and meta-analysis aim to evaluate the long-term outcomes and adverse events associated with CAR T-cell therapy in Relapsed or Refractory(r/r) B-ALL patients. Methods: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted in PubMed, Science Direct, and Cochrane Library up to June 2024, using keywords related to CAR T-cell therapy and B-ALL. Inclusion criteria included clinical trials on CAR T-cell therapy for r/r B-ALL, published in English, with at least three patients. Studies focusing on allogeneic CAR T-cells, combination therapies with HSCT or other treatments, and those not reporting on relevant outcomes were excluded. Data extraction and risk of bias assessment were independently performed by three authors using the Newcastle-Ottawa Scale (NOS). Meta-analyses were conducted using Comprehensive Meta-Analysis (CMA) V3 and Review Manager 5.4, with event rates and odds ratios as primary outcomes. Results: Out of 2,659 identified studies, 2,065 were excluded after title and abstract screening. After full-text screening and removal of duplicates, 10 studies were included in the qualitative and quantitative analysis. These studies collectively enrolled 1,367 participants, primarily pediatric and young adults, with a median age of 14.2 years (range 0-30.4). Male participants comprised 54.2% of the population. The most common CAR T-cell therapy targeted CD19, used in 8 studies (80%), followed by anti-CD22 in 1 study (10%) and a combination of CD19/CD22 in 1 study (10%). The pooled analysis demonstrated a high rate of minimal residual disease-negative complete remission (MRD-CR), with an overall event rate of 70% (95% CI: 61% to 78%, I² = 88.35%). Anti-CD19 CAR T-cell therapy showed the highest efficacy with an event rate of 74.75% (95% CI: 61% to 80%, I² = 89.84%). Combination therapies targeting both CD19 and CD22 had an event rate of 69% (95% CI: 53% to 83%, I² = 82.56%). Significant adverse effects were noted, including Cytokine Release Syndrome (CRS) with a mean incidence of 81.8% (95% CI: 76.7% to 86.9%), neurotoxicity at 33.2% (95% CI: 28.1% to 38.3%), and hematologic toxicities at 71.9% (95% CI: 66.4% to 77.4%). Discussion: CAR T-cell therapy, particularly anti-CD19, shows substantial efficacy in achieving MRD-CR in r/r B-ALL patients. The combination of CD19 and CD22 targeting CAR T-cells further enhances efficacy, addressing antigen escape. Despite high efficacy, significant adverse effects, such as CRS, neurotoxicity, and hematologic toxicities, necessitate effective management strategies. The variability in study designs, patient populations, and CAR T-cell constructs among included studies contributed to high heterogeneity. This underscores the need for standardized protocols and large-scale, multi-center trials to validate and extend these findings. Conclusion: CAR T-cell therapy represents a groundbreaking advancement in treating r/r B-ALL, offering high rates of durable remissions. However, the associated significant adverse effects require careful management. Future research should focus on optimizing CAR T-cell constructs, refining treatment protocols, and conducting large-scale, multi-center trials to improve patient outcomes. Continued advancements in CAR T-cell therapy have the potential to transform B-ALL treatment, providing durable remissions and improved survival for patients with limited treatment options.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.031 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.019 | 0.044 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".