Prognostic significance of CD30 expression in diffuse large B‐cell lymphoma: A systematic review with meta‐analysis

Rodrigues-Fernandes, Carla Isabelly; Abreu, Lucas Guimarães; Radhakrishnan, Raghu; Pérez, Danyel Elias da Cruz; Amaral‐Silva, Gleyson Kleber do; Gondak, Rogério; Rahimi, Siavash; Brennan, Peter A.; Fonseca, Felipe Paiva; Vargas, Pablo Agustı́n

doi:10.1111/jop.13208

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…For de novo EBV-negative DLBCL NOS, CD30 positivity, defined by a cut-off of 20% stained lymphoma cells, ranges from 10% to 21% across different studies, with a suggested trend toward better prognosis, especially in the GCB subgroup [ 97 , 98 , 99 , 100 ]. Conversely, utilizing a threshold of 5%, CD30 positivity is documented in up to 90% of cases of EBV-positive non-GC DLBCL, correlating with worse outcomes in this subset [ 101 , 102 ].…”

Section: Anti-cd30 Antibody–drug Conjugate Brentuximab–vedotinmentioning

confidence: 99%

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

D’Alò,

Bellesi,

Maiolo

et al. 2024

Cancers

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Since the introduction of rituximab in the late 1990s, significant progress has been made in advancing targeted therapies for B cell lymphomas, improving patients’ chance of being cured and clinicians’ therapeutic armamentarium. A better understanding of disease biology and pathogenic pathways, coupled with refinements in immunophenotypic and molecular diagnostics, have been instrumental in these achievements. While traditional chemotherapy remains fundamental in most cases, concerns surrounding chemorefractoriness and cumulative toxicities, particularly the depletion of the hemopoietic reserve, underscore the imperative for personalized treatment approaches. Integrating targeted agents, notably monoclonal antibodies, alongside chemotherapy has yielded heightened response rates and prolonged survival. A notable paradigm shift is underway with innovative-targeted therapies replacing cytotoxic drugs, challenging conventional salvage strategies like stem cell transplantation. This review examines the landscape of emerging targets for lymphoma cells and explores innovative therapies for diffuse large B cell lymphoma (DLBCL). From Chimeric Antigen Receptor-T cells to more potent monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, checkpoint inhibitors, and small molecules targeting intracellular pathways, each modality offers promising avenues for therapeutic advancement. This review aims to furnish insights into their potential implications for the future of DLBCL treatment strategies.

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Section: Anti-cd30 Antibody–drug Conjugate Brentuximab–vedotinmentioning

confidence: 99%

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

D’Alò,

Bellesi,

Maiolo

et al. 2024

Cancers

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“…This antigen belongs to TNF receptor superfamily, and CD30 signaling is involved in regulation of cytokine secretion, cell proliferation and survival [ 326 ]. CD30 is highly expressed in most B-NHL [ 326 , 327 , 328 ]. Brentuximab vedotin, an ADC comprising a human anti-CD30 chimeric Ab covalently bound to the microtubule-disrupting agent monomethyl auristatin E, was approved in R/R B-NHL after autologous stem cell transplantation and anaplastic large-cell lymphoma [ 326 ].…”

Section: Clinical Trials Of Novel Anti-taa Inhibitors In the Treatmen...mentioning

confidence: 99%

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Tannoury

Garnier

Susin

et al. 2022

Cancers

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Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders.

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“…CD30 is variably expressed in DLBCL, at a frequency of up to 60% depending on cut-off value [ 4 , 108 ], but unexpectedly, some studies have suggested that the response to brentuximab vedotin treatment does not correlate with CD30 expression [ 109 ]. This has led to a hypothesis that CD30-positive extracellular vesicles can transport brentuximab vedotin to CD30-negative tumor cells (a theory that is borne out by preclinical data) [ 109 ].…”

Section: Targeting Cd30 In Other Lymphomasmentioning

confidence: 99%

“…Highest CD30 expression is observed in classic Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) [ 1 ]. Variable expression is observed across other lymphomas, including peripheral T-cell lymphomas (PTCL) [ 2 ], some cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) [ 3 ], and some B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) [ 4 ] (Table 1 ). CD30-positivity, typically measured by immunohistochemistry in tissue specimens, is defined as expression levels of ≥ 75% for ALCL; however, specific cut-offs for other tumor types are not universally defined, due to variability in expression levels [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-CD30 antibody–drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

et al. 2022

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CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody–drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years.

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Prognostic significance of CD30 expression in diffuse large B‐cell lymphoma: A systematic review with meta‐analysis

Abstract: Special issue "Lymphomas and lymphoid lesions of the oral cavity".

Cited by 8 publications

References 25 publications

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Anti-CD30 antibody–drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

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