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Allogeneic CAR T-Cell Therapy Well-Tolerated and Effective Across B-Cell Malignancies

A recent meta-analysis reviewed data across 146 patients in 9 clinical trials.

A review of allogeneic chimeric antigen receptor (CAR) T-cell therapy in B-cell malignancies has revealed acceptable efficacy and safety in this population.

Findings from the meta-analysis were presented at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois by Asmi Chattaraj, MD, internal medicine resident, University of Pittsburgh Medical Center.

“Immunotherapy with CAR T-cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape,” Chattaraj and colleagues wrote. “Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system."

Chattarj and colleagues conducted a systematic literature search throughout PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, filtering with MeSH terms and keywords for B cell malignancies and CD19 targeted CAR-T therapy.

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The investigators screened data from conferences and previous systematic reviews and altogether retrieved 1247 articles and data from 146 patients in 9 clinical trials. The most common malignancy, affecting 125 patients (86%) was acute lymphoblastic leukemia. Patients’ median ages ranged from 19 to 49 years and cell doses ranged from 0.4×106 to 5×108 cells/kg.

They then pooled outcomes including complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS) with the Freeman-Tukey double arcsine transformation a random effects model in OpenMetaAnalyst software.

Chattaraj and colleagues found that 93 patients had a CR, with a pooled rate of 63% (95% CI, 47.4-78.6; I2, 78.5). The pooled rate of OS was 57.3% (95% CI, 30.8-82; I2, 79.2). In looking at adverse events, they found that pooled rate of GVHD was 9.4% (95% CI, 3.1-15.6; I2, 47.6), pooled CRS rate was 59.3% (95% CI, 30.5-88.1; I2, 95.2%) and pooled ICANS rate was 15.4% (95% CI, 4.6-26.3; I2, 72.7).

“Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up,” Chattaraj and colleagues concluded.

To read more coverage of ASCO 2022, click here.

REFERENCE
Chattaraj A, Ebad Ur Rehman M, Khan I, et al. Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: A systematic review and meta-analysis. Presented at: 2022 ASCO Meeting, June 3-7; Chicago, IL. Abstract # e19530