Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial

Diefenbach, Catherine; Hong, Fangxin; Ambinder, Richard F.; Cohen, Jonathon B.; Robertson, Michael J.; David, Kevin A.; Advani, Ranjana H.; Fenske, Timothy S.; Barta, Stefan K.; Palmisiano, Neil; Svoboda, Jakub; Morgan, David S.; Karmali, Reem; Sharon, Elad; Streicher, Howard; Kahl, Brad S.; Ansell, Stephen M.

doi:10.1016/s2352-3026(20)30221-0

Cited by 105 publications

(83 citation statements)

References 28 publications

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“…In addition to these microenvironment-based strategies, HRS-directed therapies may potentiate PD-1 blockade as well. In particular, regimens based on the combination of nivolumab with the anti-CD30 immunoconjugate brentuximab vedotin have recently been tested and may represent an effective chemo-free option for R/R patients or for those unsuitable for chemotherapy [ 103 ]. Interestingly, CD30 can be released by HRS cells either through the shedding of its ectodomain (sCD30) or loaded on extracellular vesicles (EV).…”

Section: Translational Insights To Improve Immunotherapy Resultsmentioning

confidence: 99%

The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment

Ferrarini

Rigo

Visco

et al. 2020

Cancers

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Classic Hodgkin lymphoma (cHL) is a unique lymphoid neoplasm characterized by extensive immune infiltrates surrounding rare malignant Hodgkin Reed–Sternberg (HRS) cells. Different subsets of T and NK cells have long been recognized in the cHL microenvironment, yet their distinct contribution to disease pathogenesis has remained enigmatic. Very recently, novel platforms for high dimensional analysis of immune cells, such as single-cell RNA sequencing and mass cytometry, have revealed unanticipated insights into the composition of T- and NK-cell compartments in cHL. Advances in imaging techniques have better defined specific T-helper subpopulations physically interacting with neoplastic cells. In addition, the identification of novel cytotoxic subsets with an exhausted phenotype, typically enriched in cHL milieu, is shedding light on previously unrecognized immune evasion mechanisms. This review examines the immunological features and the functional properties of T and NK subsets recently identified in the cHL microenvironment, highlighting their pathological interplay with HRS cells. We also discuss how this knowledge can be exploited to predict response to immunotherapy and to design novel strategies to improve PD-1 blockade efficacy.

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Section: Translational Insights To Improve Immunotherapy Resultsmentioning

confidence: 99%

The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment

Ferrarini

Rigo

Visco

et al. 2020

Cancers

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show abstract

“…Finally, a recent phase I/II trial assessed the combination of BV with either nivolumab, ipilimumab, or both (triplet therapy) in the r/r disease setting [ 192 ]. ORRs were similar between the three groups at 89%, 76%, and 82%, respectively.…”

Section: Engaging the Antitumor Immune Responsementioning

confidence: 99%

Engaging the Innate and Adaptive Antitumor Immune Response in Lymphoma

Csizmar

Ansell

2021

IJMS

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Immunotherapy has emerged as a powerful therapeutic strategy for many malignancies, including lymphoma. As in solid tumors, early clinical trials have revealed that immunotherapy is not equally efficacious across all lymphoma subtypes. For example, immune checkpoint inhibition has a higher overall response rate and leads to more durable outcomes in Hodgkin lymphomas compared to non-Hodgkin lymphomas. These observations, combined with a growing understanding of tumor biology, have implicated the tumor microenvironment as a major determinant of treatment response and prognosis. Interactions between lymphoma cells and their microenvironment facilitate several mechanisms that impair the antitumor immune response, including loss of major histocompatibility complexes, expression of immunosuppressive ligands, secretion of immunosuppressive cytokines, and the recruitment, expansion, and skewing of suppressive cell populations. Accordingly, treatments to overcome these barriers are being rapidly developed and translated into clinical trials. This review will discuss the mechanisms of immune evasion, current avenues for optimizing the antitumor immune response, clinical successes and failures of lymphoma immunotherapy, and outstanding hurdles that remain to be addressed.

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“…The lymphocyte activation gene-3 (LAG-3) molecule is on the cell surface of activated CD4+ and CD8+ effector T cells, CD4+FOXP3+ Treg, Tr1 cells, B cells, plasmacytoid dendritic cells and NK cells. It structurally resembles the CD4 coreceptor and binds to MHC class II with high affinity [ 122 , 123 ]. LAG-3 acts synergistically with PD-1 and/or CTLA-4 to negatively regulate T cell expansion and LAG-3+ T cells populate cHL ME in most of the cases [ 115 , 124 , 125 , 126 ].…”

Section: Hrcs Escape the Immunosurveillancementioning

confidence: 99%

Immune Microenvironment Features and Dynamics in Hodgkin Lymphoma

Bertuzzi

Sabattini

Agostinelli

2021

Cancers

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Classical Hodgkin’s lymphoma (cHL) accounts for 10% of all lymphoma diagnosis. The peculiar feature of the disease is the presence of large multinucleated Reed–Sternberg and mononuclear Hodgkin cells interspersed with a reactive microenvironment (ME). Due to the production of a large number of cytokines, Hodgkin cells (HCs) and Hodgkin Reed–Sternberg cells (HRSCs) attract and favour the expansion of different immune cell populations, modifying their functional status in order to receive prosurvival stimuli and to turn off the antitumour immune response. To this purpose HRSCs shape a biological niche by organizing the spatial distribution of cells in the ME. This review will highlight the contribution of the ME in the pathogenesis and prognosis of cHL and its role as a possible therapeutic target.

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Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial

Cited by 105 publications

References 28 publications

The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment

The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment

Engaging the Innate and Adaptive Antitumor Immune Response in Lymphoma

Immune Microenvironment Features and Dynamics in Hodgkin Lymphoma

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