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Review
. 2024 Sep 10;8(17):4700-4710.
doi: 10.1182/bloodadvances.2021004535.

The rules of T-cell engagement: current state of CAR T cells and bispecific antibodies in B-cell lymphomas

J Erika Haydu  1   2 , Jeremy S Abramson  1   2
Affiliations
Review

The rules of T-cell engagement: current state of CAR T cells and bispecific antibodies in B-cell lymphomas

J Erika Haydu et al. Blood Adv. .

Abstract

T-cell engaging-therapies have transformed the treatment landscape of relapsed and refractory B-cell non-Hodgkin lymphomas by offering highly effective treatments for patients with historically limited therapeutic options. This review focuses on the advances in chimeric antigen receptor-modified T cells and bispecific antibodies, first providing an overview of each product type, followed by exploring the primary data for currently available products in large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. This review also highlights key logistical and sequencing considerations across diseases and product types that can affect clinical decision-making.

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Conflict of interest statement

Conflict-of-interest disclosure: J.E.H. reports consulting for Genmab and research funding (to institution) from Genmab. J.S.A. reports consulting for AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb (BMS), Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, Roche, Seagen, and Takeda, and research support (to institution) from BMS, Celgene, Cellectis, Genentech, Merck, Mustang Bio, Regeneron, Seagen, and Takeda.

Figures

Figure 1.
Figure 1.
CAR T cells and BsAbs target lymphoma cells through distinct T-cell–mediated mechanisms of action. (A) Currently approved CAR T cells in B-cell lymphomas are generated from autologous T cells engineered to express an antigen receptor targeting CD19 on lymphoma cells, as well as a transmembrane spacer, a costimulatory domain, and an intracellular signaling domain, which together drive T-cell activation and ultimately lymphoma cell destruction. (B) Currently approved BsAb in B-cell lymphomas are off-the-shelf antibodies targeting CD3 on endogenous T cells and CD20 on lymphoma cells, bringing the 2 entities together to result in T-cell–mediated lymphoma cell death.
Figure 2.
Figure 2.
Comparison of CAR T-cell and BsAb characteristics. CAR T cells and BsAbs are associated with unique considerations regarding logistics and toxicity. NT, neurologic toxicity.
Figure 3.
Figure 3.
Sequencing treatments in LBCL. Flowchart outlines a proposed sequencing of therapies in LBCL based on current approvals and highlighting when to consider CAR T cells and/or BsAbs. GCB, germinal center B cell; Lonca, loncastuximab tesirine; PMBCL (primary mediastinal B-cell lymphoma); Pola-BR, polatuzumab vedotin, bendamustine rituximab; R-GemOx, rituximab, gemcitabine, oxaliplatin; Tafa/len, tafasitamab/lenalidomide.
Figure 4.
Figure 4.
Sequencing treatments in FL and MCL. Flow charts outline a proposed sequencing of therapies in FL and MCL based on current approvals and highlighting when to consider CAR T-cells and/or BsAb. In R/R FL, patients should again have an indication for therapy to proceed to next line of treatment. ^This approach is based on the TRIANGLE study. In situations in which 1L ibrutinib is not available, recommend treatment with cytarabine-containing induction chemoimmunotherapy followed by maintenance rituximab and replacement of ibrutinib with another covalent BTKi if possible. BR, bendamustine rituximab; CD20 Ab, CD20 antibody; RBAC, rituximab, bendamustine, cytarabine.
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References

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