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Review
. 2022 Jul 6:13:904497.
doi: 10.3389/fimmu.2022.904497. eCollection 2022.

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

Ana Carolina Caballero  1   2   3   4 , Laura Escribà-Garcia  1   2   3 , Carmen Alvarez-Fernández  1   2   3 , Javier Briones  1   2   3   4
Affiliations
Review

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

Ana Carolina Caballero et al. Front Immunol. .

Abstract

Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed.

Keywords: CAR-T; DLBCL; antibodies; bispecific; lymphoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Illustration of the evolution of chimeric receptors design. Fragments from the native TCR-CD3 complex and antibodies were joined into fusion proteins that were improved to reach the basic structure of the second-generation CARs, which were successfully brought to the clinic. At the bottom, the figure shows the critical differences between the three FDA-approved second-generation CAR constructs.
Figure 2
Figure 2
Summary of main factors influencing the efficacy of CART19 therapy.
Figure 3
Figure 3
Management proposal for patients with R/R DLBCL who fail CART19 treatment. Novel clinically relevant therapies based on CD19 tumor expression are shown. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; BR, bendamustine-rituximab.
See this image and copyright information in PMC

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