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Curated Papers > In recent years, high-impact research on "single-cell sequencing" (IF≥30, past 5 years)

The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management. ​

Literature Information ​

DOI10.3322/caac.21589
PMID31815293
JournalCA: a cancer journal for clinicians
Impact Factor232.4
JCR QuartileQ1
Publication Year2020
Times Cited36
Keywordsmanagement, novel treatment, peripheral T-cell lymphoma, standard therapy
Literature TypeJournal Article, Review
ISSN0007-9235
Pages47-70
Issue70(1)
AuthorsEnrica Marchi, Owen A O'Connor

TL;DR ​

This research highlights the historical neglect of peripheral T-cell lymphomas (PTCLs), which account for 6-10% of non-Hodgkin lymphoma cases and have seen minimal improvement in treatment outcomes compared to B-cell lymphomas. Recent advancements in drug approvals and a better understanding of PTCL's molecular pathogenesis are paving the way for novel targeted therapies that may significantly enhance treatment paradigms for these rare and heterogeneous malignancies.

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management · novel treatment · peripheral T-cell lymphoma · standard therapy

Abstract ​

Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.

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Primary Questions Addressed ​

  1. What are the key molecular mechanisms driving the heterogeneity of peripheral T-cell lymphomas (PTCLs)?
  2. How do the recent drug approvals for PTCL compare in efficacy to traditional chemotherapy treatments?
  3. What specific challenges do clinicians face when treating the various subtypes of PTCL?
  4. In what ways might epigenetic modifiers influence the treatment landscape for mature T-cell lymphomas?
  5. How can the lessons learned from B-cell lymphoma treatment advancements be applied to improve outcomes in PTCL patients?

Key Findings ​

Key Insights ​

1. Research Background and Objectives: The study focuses on the historical challenges faced in the treatment of mature T-cell lymphoma (MTCL), particularly peripheral T-cell lymphomas (PTCLs), which represent a small fraction (6% to 10%) of total non-Hodgkin lymphoma (NHL) cases. Despite the significant advancements in the management of B-cell lymphomas over the past few decades, PTCLs have not seen similar progress, primarily due to their rarity and heterogeneous nature, with 29 distinct subtypes identified by the WHO in 2017. The objective of this research is to highlight the evolving landscape in PTCL biology and management, emphasizing recent developments in drug approvals and molecular understanding of the disease.

2. Main Methods and Findings: The authors reviewed historical data, drug approval timelines, and advances in molecular biology related to PTCLs. They noted that previous treatment paradigms for PTCL were predominantly based on therapies developed for B-cell neoplasms, which do not adequately address the unique characteristics of T-cell malignancies. The study highlights that the first drug specifically approved for PTCL was introduced only a decade ago. Recent advancements include a surge in novel drug approvals and a deeper understanding of the disease's molecular pathogenesis, leading to innovative research focused on developing targeted small molecules, epigenetic modifiers, and biologics.

3. Core Conclusions: The research concludes that the recent influx of new therapies and improved comprehension of PTCL biology marks a significant turning point in the management of this challenging subset of lymphomas. These developments provide hope for better treatment outcomes and challenge the longstanding reliance on chemotherapy paradigms that have proven inadequate for T-cell malignancies. The authors emphasize that targeted therapies may soon replace traditional chemotherapy approaches, potentially improving prognosis for patients with PTCL.

4. Research Significance and Impact: This research is significant as it underscores the need for a paradigm shift in the treatment of PTCLs, advocating for strategies that consider the unique biological characteristics of T-cell lymphomas. The identification of novel therapeutic targets and the development of specialized drugs could lead to more effective treatment options, ultimately improving patient outcomes and survival rates. By shedding light on the complexities of PTCLs and the advancements in targeted therapy, this work has the potential to influence future clinical practices and research directions in hematologic malignancies, paving the way for personalized medicine approaches in the treatment of rare and heterogeneous cancers.

Literatures Citing This Work ​

  1. Rituximab Plus Chemotherapy Provides No Clinical Benefit in a Peripheral T-Cell Lymphoma Not Otherwise Specified with Aberrant Expression of CD20 and CD79a: A Case Report and Review of the Literature. - Alessandro Mangogna;Maria Christina Cox;Luigi Ruco;Gianluca Lopez;Beatrice Belmonte;Arianna Di Napoli - Diagnostics (Basel, Switzerland) (2020)
  2. Clinical Remission in a 72-Year-Old Patient with a Massive Primary Cutaneous Peripheral T-Cell Lymphoma-NOS of the Eyelid, Following Combination Chemotherapy with Etoposide Plus COP. - Sabina Iluta;Dragos-Alexandru Termure;Bobe Petrushev;Bogdan Fetica;Mindra-Eugenia Badea;Madalina Moldovan-Lazar;Manuela Lenghel;Csaba Csutak;Andrei Roman;Sergiu Pasca;Alina-Andreea Zimta;Ciprian Jitaru;Ciprian Tomuleasa;Rares-Calin Roman - Diagnostics (Basel, Switzerland) (2020)
  3. All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma. - Maria Christina Cox;Marta Banchi;Sabrina Pelliccia;Arianna Di Napoli;Luigi Marcheselli;Caterina Patti;Paola Anticoli Borza;Roberta Battistini;Francesca Di Gregorio;Paola Orlandi;Guido Bocci - Cancer chemotherapy and pharmacology (2020)
  4. B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974? - Minodora Desmirean;Sebastian Rauch;Ancuta Jurj;Sergiu Pasca;Sabina Iluta;Patric Teodorescu;Cristian Berce;Alina-Andreea Zimta;Cristina Turcas;Adrian-Bogdan Tigu;Cristian Moldovan;Irene Paris;Jakob Steinheber;Cedric Richlitzki;Catalin Constantinescu;Olafur Eysteinn Sigurjonsson;Delia Dima;Bobe Petrushev;Ciprian Tomuleasa - Journal of clinical medicine (2020)
  5. Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma. - Caiqin Xie;Xian Li;Hui Zeng;Wenbin Qian - Experimental hematology & oncology (2020)
  6. Chemotherapy Plus Radiotherapy Versus Chemotherapy Alone for Patients With Peripheral T-Cell Lymphoma, Not Otherwise Specified. - Zegeng Chen;He Huang;Xiaoqian Li;Xiaojie Fang;Zhao Wang;Huangming Hong;Zhihui Zhang;Qingqing Cai;Zhiming Li;Meiting Chen;Yuyi Yao;Fei Pan;Limin Chen;Tongyu Lin - Frontiers in oncology (2021)
  7. A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes. - Ping Zhao;Meng-Meng Ji;Ying Fang;Xiao Li;Hong-Mei Yi;Zi-Xun Yan;Shu Cheng;Peng-Peng Xu;Anne Janin;Chao-Fu Wang;Li Wang;Wei-Li Zhao - Cell death & disease (2021)
  8. Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis. - Jun Du;Dandan Yu;Xinle Han;Lijun Zhu;Zoufang Huang - JAMA network open (2021)
  9. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. - Mehdi Hamadani;Graham P Collins;Paolo F Caimi;Felipe Samaniego;Alexander Spira;Andrew Davies;John Radford;Tobias Menne;Anand Karnad;Jasmine M Zain;Paul Fields;Karin Havenith;Hans G Cruz;Shui He;Joseph Boni;Jay Feingold;Jens Wuerthner;Steven Horwitz - The Lancet. Haematology (2021)
  10. Updates in the Treatment of Peripheral T-Cell Lymphomas. - Khalil Saleh;Jean-Marie Michot;Vincent Ribrag - Journal of experimental pharmacology (2021)

... (26 more literatures)

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