AML-1276: CRISPR-Cas9 Therapies in Hematologic Malignancies: A Meta-Analysis of Clinical Outcomes, Safety, and Translational Implications

Document Type

Conference Proceeding

Publication Date

9-1-2025

Publication Title

Clin Lymphoma Myeloma Leuk

Keywords

CD7 antigen, acute myeloid leukemia, adverse drug reaction, aggressive B cell non Hodgkin lymphoma, antineoplastic activity, cancer inhibition, chimeric antigen receptor T-cell, clinical outcome, clustered regularly interspaced short palindromic repeat, conference abstract, cytokine release syndrome, drug therapy, ex vivo study, follow up, gene editing, genomic instability, hematologic malignancy, high throughput sequencing, human, immunocompetent cell, meta analysis, multiple myeloma, neurotoxicity, overall response rate, side effect, suicide gene, systematic review, T cell acute lymphoblastic leukemia, therapy

Abstract

CRISPR-based gene editing has introduced transformative possibilities in hematologic oncology, offering precise and durable immunologic interventions. With increasing adoption in early-phase trials, an integrated understanding of its efficacy and safety is essential. Objective: To evaluate the efficacy, safety, and translational potential of CRISPR-Cas9-based therapies in hematologic malignancies through a structured meta-analysis of early-phase clinical trials. Design: Systematic review and meta-analysis of CRISPR-based hematologic cancer trials published between 2019 and 2024. Random-effects modeling was used due to inter-trial heterogeneity. Setting: Academic hospitals and early-phase clinical centers conducting gene-modified cellular therapy trials. Patients or Other Participants: Nine clinical trials encompassing 80 patients with relapsed or refractory hematologic malignancies, including Tcell acute lymphoblastic leukemia (T-ALL), aggressive B-cell lymphomas, and multiple myeloma. Inclusion criteria varied by trial; most patients had exhausted standard therapies. Interventions: All studies employed ex vivo CRISPR editing of immune cells. Interventions included TRAC- and PD-1-knockout chimeric antigen receptor (CAR) T cells, universal CD7-targeted base-edited T cells, and suicide-gene modified donor lymphocytes. Products were administered as single infusions following lymphodepletion. Main Outcome Measures: Overall response rate (ORR), complete response (CR) rate, incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and detection of off-target edits. Results: The pooled ORR was 62.3% (95% CI, 50.1%–73.2%), with a CR rate of 34.6%. Base-edited CAR7 T cells achieved CR in five of nine pediatric T-ALL patients. CRS occurred in 48% of patients (mostly grade 1–2) and ICANS in ∼17%, with no grade ≥3 events. No treatment-related deaths or clinically significant off-target events were reported. Deep sequencing confirmed primarily on-target edits with rare, non-propagating chromosomal changes. Follow-up ranged from 6 to 12 months. Conclusions: CRISPR-Cas9-based therapies exhibit promising antitumor activity and a manageable safety profile in hematologic cancers. These findings support the clinical viability of gene-edited cellular therapy, especially in relapsed settings. However, larger trials and long-term data are essential to validate the durability, genomic stability, and scalability of these platforms.

Volume

25

First Page

S497

Find It @ Sladen

Share

COinS