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Lymphoma

Targeted based therapy in nodal T-cell lymphomas

Abstract

T-cell lymphomas (TCL) are a group of biologically and clinically heterogenous neoplasms derived from mature T lymphocytes. Recent findings in biology have advanced the classification of these neoplasms; however, clinical investigations based on biologic features have yet to be designed. Two biomarker-driven treatments for TCL are promising: brentuximab vedotin (BV) in combination with chemotherapy or as monotherapy is the standard treatment for newly diagnosed CD30-positive TCL and relapsed/refractory anaplastic large cell lymphoma (ALCL), while ALK inhibitors have induced responses in ALK+ ALCLs. Common genetic alterations in TCL, such as aberrations in PI3K/mTOR, JAK/STAT, and epigenetic regulators are also targetable by pathway inhibitors and HDAC/DNMT inhibitors; however, responses to these treatments as monotherapy are neither satisfactory nor durable, even in patients pre-stratified by several biomarkers. Additional work is needed to extend biology/biomarker-driven treatment in these neoplasms. As T-cell lymphomagenesis is multistep and multifactorial, trials are ongoing to evaluate combination treatments. The focus of this article is to summarize the status and the current role of targeted-based therapy in nodal TCL.

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Fig. 1: Current subtypes of nodal TCLs.

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Acknowledgements

We would like to thank Dr. Fredrick B. Hagemeister for reviewing the manuscript.

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Correspondence to Dai Chihara.

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SPI has research support from Rhizen, Seattle Genetics, Spectrum (Acrotech), Affimed, Trillium, CRISPR Therapeutics, Legend Biotech, Daiichi Sankyo, Amgen and Consultant for Daiichi Sankyo, Sanofi, Seattle Genetics and Legend Biotech and speaker for Target Oncology and Curio Science. FV has research support from CRISPR Therapeutics and from NCI (R01 CA222918).

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Chihara, D., Miljkovic, M., Iyer, S.P. et al. Targeted based therapy in nodal T-cell lymphomas. Leukemia 35, 956–967 (2021). https://doi.org/10.1038/s41375-021-01191-8

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