Efficacy and Safety of Chimeric Antigen Receptor T Cell Therapy in Chronic Lymphocytic Leukemia: A Systematic Review
Bibliographic record
Abstract
Abstract Background: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. Despite the advancements in drug therapies, CLL is largely incurable, and relapsed/refractory (R/R) patients have a very poor prognosis. Chimeric antigen receptor T (CART) cell therapy has shown promising results in B-cell malignancies. We conducted a systematic review to assess the efficacy and safety of CART cell therapy in patients with CLL. Methods: PRISMA guidelines were followed to perform the literature search and selection of articles for this systematic review. A search was performed using databases including PubMed, Cochrane, Web of Science, Embase, and clinicaltrials.gov. We used the following Mesh and Emtree terms, "Chronic lymphocytic leukemia" AND "Adoptive immunotherapy" from the inception of literature till 06/11/2021. Out of 1319 articles, we screened and included nine clinical studies (N=208) measuring the efficacy (i.e., complete response, partial response, etc.) and safety (adverse events ≥grade 3) in clinical terms. We excluded case reports, pre-clinical studies, review articles, and meta-analyses. Results: In 9 clinical studies, 158 patients with CLL were treated with anti-CD19 CART cell therapy. The range of age of the patients was 38-75 years. A high dose was used in 38 patients, and ibrutinib was added in 19 patients with CLL. The therapy was well tolerated with ≥grade 3 cytokine release syndrome (CRS) and neurological toxicity reported in 23/151 (15%) and 20/151 (13%) of the patients, respectively. Table 1. Complete response (CR), partial response (PR), and overall response (OR) were seen in 40% (54/134), 17% (22/126), and 56% (103/183). In the clinical study by Frey et al. (N=51)., progression-free survival (PFS) and ORR were significantly higher in the high dose (5x10 8 cells/kg) group as compared to the low dose (5x10 7 cells/kg) group (1.8 months vs. one month and 53% vs. 29%, respectively) without significantly increasing treatment-related adverse events (TRAE). In the clinical study by Gauthier et al. (N=38)., ORR was significantly high in the anti-CD19 CART cell therapy + ibrutinib group compared to the no ibrutinib group (83% vs. 56%). Neutropenia, infection, thrombocytopenia, leukemia, hypocalcemia, elevated ALT, and tumor lysis syndrome were common ≥grade 3 TRAEs reported in these patients (Table 1). More clinical trials are targeting CD-20, CD-137, CD-7, CD-28, ROR1, etc (Table 2). Conclusion: Anti-CD19 CART cell therapy was safe and effective in the treatment of CLL patients. A high dose of 5x10 8/kg CART cell therapy was well tolerated and had superior efficacy. Adding ibrutinib to CART cell therapy was safe and more effective than anti-CD19 CART cell therapy alone. More placebo-controlled randomized multicenter studies are needed to confirm these results. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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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 | 0.006 | 0.020 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.009 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| 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".