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Targeted based therapy in nodal T-cell lymphomas
Dai Chihara1, Milos Miljkovic2, Swaminathan P Iyer3
1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. dchihara@mdanderson.org.
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.
Insights
Targeted therapies show promise for T-cell lymphomas (TCL), with brentuximab vedotin and ALK inhibitors effective in specific subtypes. However, monotherapy targeting common genetic alterations offers limited durable responses, necessitating combination treatments for T-cell lymphomas.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- T-cell lymphomas (TCL) are diverse neoplasms of mature T lymphocytes.
- Recent biological insights have improved TCL classification, but clinical trials lag.
- Biomarker-driven treatments like brentuximab vedotin and ALK inhibitors show efficacy in specific TCL subtypes.
Purpose of the Study:
- To review the current status and role of targeted therapies in nodal T-cell lymphomas.
- To highlight the potential and limitations of biomarker-driven treatments in TCL.
- To discuss the need for combination therapies in T-cell lymphomagenesis.
Main Methods:
- Literature review of targeted therapies in nodal T-cell lymphomas.
- Analysis of biomarker-driven treatment efficacy and limitations.
- Discussion of ongoing clinical trials for combination therapies.
Main Results:
- Brentuximab vedotin is standard for CD30+ TCL and relapsed/refractory ALCL.
- ALK inhibitors show responses in ALK+ ALCL.
- Monotherapies targeting PI3K/mTOR, JAK/STAT, and epigenetic regulators yield unsatisfactory and non-durable responses.
Conclusions:
- Targeted therapies offer specific treatment avenues in TCL, but monotherapy limitations persist.
- Combination treatments are crucial for addressing the multistep nature of T-cell lymphomagenesis.
- Further research is needed to optimize biology/biomarker-driven strategies in TCL.
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