Frequent expression of <scp>CD</scp>30 in extranodal <scp>NK</scp>/<scp>T</scp>‐cell lymphoma: Potential therapeutic target for anti‐<scp>CD</scp>30 antibody‐based therapy

Kawamoto, Keisuke; Miyoshi, Hiroaki; Suzuki, Takaharu; Sasaki, Yuya; Yamada, Kyohei; Yanagida, Eriko; Muto, Reiji; Kiryu, Maiko; Sone, Hirohito; Seto, Masao; Ohshima, Koichi; Takizawa, Jun

doi:10.1002/hon.2482

Cited by 30 publications

(29 citation statements)

References 35 publications

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“…Two studies of Chinese patients with nasal type extranodal NK/T-cell lymphoma (ENKTL) showed that CD30 expression is associated with a significantly poorer prognosis over the longer term despite having no impact on initial rates of response to chemotherapy [35,36]. A study of Japanese patients with ENKTL revealed that CD30-expressing disease was more frequent in patients with non-nasal versus nasal type ENKTL but CD30 was not a prognostic factor for survival [37]. Recently, CD30 expression in the neoplastic T-cell population has been reported in cases of follicular T-cell lymphoma, which is defined as an independent disease in the WHO classification; CD30 expression may provide both a diagnostic and therapeutic marker to guide treatment [38].…”

Section: Cd30 Biology In Ptcl and Ctclmentioning

confidence: 99%

The expression of CD30 and its clinico-pathologic significance in peripheral T-cell lymphomas

Karube

Kakimoto

Tonozuka

et al. 2021

Expert Review of Hematology

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Introduction: Recent studies have shown that CD30 expression can be an important feature of peripheral and cutaneous T-cell lymphomas (PTCLs and CTCLs) and CD30 testing has increased in importance with the emergence of CD30-directed therapy.Areas covered: This article reviews the literature on CD30-related biology, prevalence, and therapy in patients with PTCL or CTCL. We searched the PubMed database from 1 January 2010 to 28 April 2020, using terms 'CD30ʹ ('peripheral T-cell lymphomas' or 'cutaneous T-cell lymphoma') and 'immunohistochemistry' or 'flow cytometry' or 'pathology,' and synonyms including terms for T-cell lymphoma subtypes. Expert opinion: CD30 is expressed at relatively high rates of prevalence across a broad range of PTCLs and CTCLs. CD30 expression may be critical to the development of a subset of PTCLs and also a biomarker for treatment choice in some subtypes. Large-scale randomized, controlled studies have shown that CD30-directed treatment with brentuximab vedotin is significantly more effective against CD30-expressing PTCL and CTCL than current standard-of-care regimens. However, accurate CD30 evaluation is limited by inconsistencies in detection methodology and expression cutoffs defining CD30-expressing disease. Greater understanding of CD30 testing and reporting will enable more patients with CD30-expressing PTCL and CTCL to be identified and treated appropriately.

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Section: Cd30 Biology In Ptcl and Ctclmentioning

confidence: 99%

The expression of CD30 and its clinico-pathologic significance in peripheral T-cell lymphomas

Karube

Kakimoto

Tonozuka

et al. 2021

Expert Review of Hematology

Self Cite

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“…The largest study included 317 ENKTCL patients and out of the 91 patients who had CD30 immunohistochemistry performed on cataloged tissue, they found no association between CD30 expression and survival outcomes ( 26 ). Similarly, the most recent study of 97 patients showed 56% of specimens had CD30 expression, but there was no association with OS or PFS at CD30 cutoffs of 1, 10, or 20% ( 28 ). These variable results are due to the retrospective nature of these studies, tumor variability with varying numbers of early versus late stage patients and different cutoffs for what constitutes positive CD30 tumor expression.…”

Section: Targeting Cd30mentioning

confidence: 96%

“…It functions as a member of the tumor necrosis factor receptor pathway and is not usually expressed in normal human tissue, which makes it an attractive tumor target ( 25 ). CD30 expression in ENKTCL is variable around 50–70% in three separate studies but its clinical significance remains controversial ( 26 – 28 ). In one 22-patient study, CD30 expression of ≥50% was associated with worse event-free survival and OS ( 29 ).…”

Section: Targeting Cd30mentioning

confidence: 99%

Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma

Oki

2018

Front. Oncol.

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Extranodal NK/T-cell lymphoma (ENKTCL) is a highly aggressive mature NK/T-cell neoplasm marked by NK-cell phenotypic expression of CD3ε and CD56. While the disease is reported worldwide, there is a significant geographic variation with its highest incidence in East Asian countries possibly related to the frequent early childhood exposure of Epstein–Barr virus (EBV) and specific ethnic–genetical background, which contributes to the tumorigenesis. Historically, anthracycline-based chemotherapy such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) was used, but resulted in poor outcomes. This is due in part to intrinsic ENKTCL resistance to anthracycline caused by high expression levels of P-glycoprotein. The recent application of combined modality therapy with concurrent or sequential radiation therapy for early stage disease, along with non-anthracycline-based chemotherapy regimens consisting of drugs independent of P-glycoprotein have significantly improved clinical outcomes. Particularly, this neoplasm shows high sensitivity to l-asparaginase as NK-cells lack asparagine synthase activity. Even still, outcomes of patients with advanced stage disease or those with relapsed/recurrent disease are dismal with overall survival of generally a few months. Thus, novel therapies are needed for this population. Clinical activity of targeted antibodies along with antibody–drug conjugates, such as daratumumab (naked anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody conjugated with auristatin E), have been reported. Further promising data have been shown with checkpoint inhibitors as high levels of programmed death-ligand 1 expression are observed in ENKTCL due to EBV-driven overexpression of the latent membrane proteins [latent membrane protein 1 (LMP1) and LMP2] with activation of the NF-κB/MAPK pathways. Initial case series with programmed death 1 inhibitors showed an overall response rate of 100% in seven relapsed patients including five with a complete response (CR). Furthermore, cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 have shown encouraging results with durable CRs as either maintenance therapy after initial induction chemotherapy or in the relapsed/refractory setting. In this paper, we review this exciting field of novel immunotherapy options against ENKTCL that hopefully will change the treatment paradigm in this deadly disease.

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“…The CD30 expression rate in ENKTCL is reported to be around 50–70% in different studies [ 76 - 78 ]. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, induced CR in two patients with refractory ENKTL as a single agent or in combination with bendamustine [ 79 , 80 ].…”

Section: Novel Approachesmentioning

confidence: 99%

Extranodal NK/T cell lymphoma

Jeong

2020

Blood Res

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Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a distinct subtype of Non-Hodgkin's lymphoma mainly involving the nasal area. Since the entity was first recognized, treatment strategies have been evolving from anthracycline-based chemotherapy and radiotherapy to L-asparaginase containing regimens and recently immune checkpoint inhibitors. With the currently used combined chemotherapy and radiotherapy, more than 70% of patients with localized disease can be cured. L-asparaginase containing regimens have significantly improved treatment outcomes among patients with advanced disease. However, the treatment outcomes of patients with disease refractory to L-asparaginase containing regimens or who experience recurrence remain poor. In this article, we cover the current treatments for ENKTL and emerging treatment approaches.

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Frequent expression of CD30 in extranodal NK/T‐cell lymphoma: Potential therapeutic target for anti‐CD30 antibody‐based therapy

Cited by 30 publications

References 35 publications

The expression of CD30 and its clinico-pathologic significance in peripheral T-cell lymphomas

The expression of CD30 and its clinico-pathologic significance in peripheral T-cell lymphomas

Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma

Extranodal NK/T cell lymphoma

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