Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis

Author:

Yarza Ramon1ORCID,Bover Mateo1,Herrera-Juarez Mercedes1,Rey-Cardenas Macarena1,Paz-Ares Luis1,Lopez-Martin Jose A23,Haanen John4

Affiliation:

1. Department of Medical Oncology, Hospital Universitario 12 de Octubre , Madrid , Spain

2. Virology and Inflammation Unit, PharmaMar , SA, Madrid , Spain

3. GETICA (Spanish Group for Cancer Immuno-Biotherapies) , Madrid , Spain

4. Division of Medical Oncology, Netherlands Cancer Institute , Amsterdam , The Netherlands

Abstract

Abstract Background T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma. Methods We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response. Results From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007). Conclusion TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference28 articles.

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