The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma

Horwitz, Steven M.; O’Connor, Owen A.; Pro, Barbara; Trümper, Lorenz; Iyer, Swaminathan P.; Advani, Ranjana H.; Bartlett, Nancy L.; Christensen, Jacob Haaber; Morschhauser, Franck; Domingo‐Domènech, Eva; Rossi, Giuseppe; Kim, Woo Seob; Feldman, Tatyana; Menne, Tobias; Belada, David; Illés, Árpád; Tobinai, Kensei; Tsukasaki, Kunihiro; Yeh, Su‐Peng; Shustov, Andrei R.; Hüttmann, Andreas; Savage, Kerry J.; Yuen, Sam; Zinzani, Pier Luigi; Miao, Harry; Bunn, Veronica; Fenton, Keenan; Fanale, Michelle A.; Puhlmann, Markus; Illidge, Tim

doi:10.1016/j.annonc.2021.12.002

Cited by 134 publications

(117 citation statements)

References 38 publications

(67 reference statements)

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“…The recent identification and development of brentuximab vedotin (BV), an antibody–drug conjugate (ADC) consisting of a monoclonal antibody targeting CD30 coupled to the microtubule inhibitor monomethyl auristatin E (MMAE), represents a major milestone in the treatment of PTCL. The results of the ECHELON-2 study demonstrated that BV combined with CHP could provide clinically meaningful improvement as a first-line treatment for PTCL, achieving a 5-years PFS rate of 51.4% and a 5-years OS rate of 70.1% ( Horwitz et al, 2022 ).…”

Section: Current Status Of Peripheral T-cell Lymphoma Treatmentmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

Chen

Wei

et al. 2022

Front. Pharmacol.

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Peripheral T-cell lymphomas (PTCLs) are highly heterogeneous and present significant treatment challenges. Immune checkpoint therapies, such as PD-1 and CTLA-4 inhibitors, have significantly changed the clinical management paradigm of tumors. The roles of immune checkpoints in PTCL and related agents have been actively explored over recent years. PD-1 and PD-L1 expression is detectable in both PTCL and immune cells within the tumor microenvironment and forms the basis for the exploration of antibodies targeting these proteins. Such antibodies are currently being investigated in clinical trials to guide individualized therapy. PD-1/PD-L1 inhibitors alone and in combination with chemotherapy, radiotherapy, or targeted therapy have shown broad clinical efficacy and improved the survival of cancer patients. Studies of other immune checkpoint proteins, such as CTLA-4, TIM-3, LAG-3, and TIGIT, are likely to provide potential novel targets for immunotherapy. Here, we review the role of and recent advances in immune checkpoint blockade in common subtypes of PTCL, focusing on the anti-tumor immune responses to PD-1/PD-L1 blockers.

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Section: Current Status Of Peripheral T-cell Lymphoma Treatmentmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

Chen

Wei

et al. 2022

Front. Pharmacol.

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“…From the 5-year updated intention to treat analyses, frontline treatment with BV + CHP yielded superior outcomes as compared to CHOP. At the median follow-up of 47.6 months, 5-year PFS was 51.4% with BV + CHP vs. 43.0% with CHOP, and 5-year overall survival (OS) rates were 70.1% with BV + CHP vs 61.0% with CHOP [25]. Comparable efficacy was also observed among patients who relapsed and subsequently received BV monotherapy, with an ORR of 59% in patients retreated following BV + CHP as compared to 50% following CHOP.…”

Section: Brentuximab Vedotinmentioning

confidence: 99%

“…Comparable efficacy was also observed among patients who relapsed and subsequently received BV monotherapy, with an ORR of 59% in patients retreated following BV + CHP as compared to 50% following CHOP. Although ECHELON-2 was not powered to directly compare BV + CHP vs. CHOP among non-ALCL subgroups, responses trending towards superiority were observed in the major PTCL subtypes (despite wide confidence intervals) and were statistically significant in both ALK-positive and ALK-negative ALCL [25]. Adverse events (AEs) were generally similar between treatment arms, with peripheral sensory neuropathy reported in 52% of patients receiving BV + CHP and 55% of patients receiving CHOP.…”

Section: Brentuximab Vedotinmentioning

confidence: 99%

Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas

Angelos

Ballard

Barta

2022

JPM

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Peripheral T-cell lymphomas (PTCLs) are a rare and heterogenous subset of non-Hodgkin lymphoma characterized by an aggressive clinical course. Historically, the treatment of PTCLs have been analogous to that of aggressive B-cell lymphomas; however, it has been well-established that overall responses and complete remission rates are far inferior using near-identical chemotherapy strategies. Recently, there has been a plethora of newer agents designed to target distinguishing cellular and molecular features of specific PTCL subtypes. These agents have been proven to yield superior anti-lymphoma responses and, in some cases, overall survival in the relapsed, refractory, and frontline treatment setting. In this review, we will summarize and highlight the most influential clinical trials leading to the Food and Drug Administration (FDA) approval of several novel therapeutic agents against PTCL, with an emphasis on emerging studies and strategies to expand their potential use in the frontline treatment setting.

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“…Given evidence of multidrug resistance by expression in relapsed and refractory lymphoma, prolonged exposure to doxorubicin and vincristine over a 4-day infusion may overcome resistance mechanism compared to the 1-day infusion used in CHOP [53] . In the phase II study of dose-adjusted Infusional etoposide, doxorubicin, and vincristine with cyclophosphamide and prednisone (EPOCH), 41 previously untreated patients with PTCL (excluding ATLL) were treated, leading to an ORR of 78% (with 61% achieving a complete response [CR]).…”

Section: Infusional Etoposide Doxorubicin and Vincristine With Cyclop...mentioning

confidence: 99%

The peripheral T-cell lymphoma: can we pivot from the chemotherapy-predicated paradigm?

Ma¹,

Marchi²

2022

J Cancer Metastasis Treat

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Peripheral T-cell lymphomas (PTCL) are uncommon and aggressive diseases that are difficult to study. Combination chemotherapy such as cyclophosphamide, doxorubicin, vincristine, and prednisone has been the mainstay of treatment for almost 30 years, but outcomes remain poor. The development of new targeted therapies is changing the landscape of how we treat patients with these difficult diseases. For instance, the addition of brentuximab vedotin to combination chemotherapy enhanced the outcomes in patients with CD30-positive anaplastic large cell lymphomas, but there is still a need for better therapies in the other numerous subtypes. Here we discuss the data for the existing treatment paradigm of PTCL as well as the merits of shifting toward a chemotherapy-free approach.

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The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma

Cited by 134 publications

References 38 publications

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas

The peripheral T-cell lymphoma: can we pivot from the chemotherapy-predicated paradigm?

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