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Non-Hodgkin Lymphoma
Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas
Ferrata Storti Foundation
Haematologica 2021 Volume 106(6):1705-1713
Jakub Svoboda,1 Steven M. Bair,1 Daniel J. Landsburg,1 Sunita Dwivedy Nasta,1 Sarah J. Nagle,2 Stefan K. Barta,1 Nadia Khan,3 Joanne Filicko-O'Hara,4 Sameh Gaballa,4 Lauren Strelec,1 Elise Chong,1 Sheryl Mitnick,1 Terease S. Waite,1 Cara King,1 Hatcher Ballard,1 Matthew Youngman,1 James Gerson,1 John P. Plastaras,1 Amit Maity,1 Agata M. Bogusz,1 Stacy S. Hung,5 Hisae Nakamura,5 Reza Nejati,3 Christian Steidl,5 Megan Lim,1 Marco Ruella1 and Stephen J. Schuster1
1University of Pennsylvania, Philadelphia, PA, USA; 2Oregon Health and Science University, Portland, OR, USA: 3Fox Chase Cancer Center, Philadelphia, PA, USA; 4Thomas Jefferson University, Philadelphia, PA, USA and 5Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada
ABSTRACT
We conducted a phase I/II multicenter trial using six cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment of patients with CD30-positive B-cell lymphomas. Thirty-one patients were evaluable for toxicity and 29 for efficacy including 22 with primary mediastinal B-cell lymphoma, five with diffuse large B-cell lym- phoma, and two with gray zone lymphoma. There were no treatment- related deaths; 32% of patients had non-hematologic grade 3/4 toxici- ties. The overall response rate was 100% (95% confidence interval [95% CI]: 88-100) with 86% (95% CI: 68-96) of patients achieving complete response at the end of systemic treatment. Consolidative radiation fol- lowing end-of-treatment response assessment was permissible and used in 52% of all patients including 59% of the patients with primary medi- astinal B-cell lymphoma. With a median follow-up of 30 months, the 2- year progression-free survival and overall survival rates were 85% (95% CI: 66-94) and 100%, respectively. In the cohort with primary mediasti- nal B-cell lymphoma, the 2-year progression-free survival rate was 86% (95% CI: 62-95). In summary, BV-R-CHP with or without consolidative radiation is a feasible and active frontline regimen for CD30-positive B- cell lymphomas (ClinicalTrials.gov identifier: NCT01994850).
Introduction
Brentuximab vedotin (BV) is an immunoconjugate consisting of a CD30-directed antibody linked to the anti-microtubule agent auristatin.1 BV is highly active in relapsed and refractory (r/r) classical Hodgkin lymphoma and in CD30-expressing T-cell lymphomas.2,3 In the frontline setting, BV combined with chemotherapy has been recently approved for advanced classical Hodgkin lymphoma and CD30-pos- itive (CD30+) T-cell lymphomas based on results of randomized trials showing ben- efit of the BV-containing arms.4,5
BV targets the cell membrane protein CD30 that is expressed not only by classi- cal Hodgkin lymphoma and some T-cell lymphomas, but at various frequencies also by B-cell non-Hodgkin lymphomas including up to 80% of primary mediasti- nal B-cell lymphomas (PMBCL).6-9 PMBCL is a mature large B-cell lymphoma of thymic origin which usually presents with mediastinal masses. It occurs predomi- nantly in young adults and represents about 5% of aggressive B-cell lymphomas.10 While previous classifications considered it as a subtype of diffuse large B-cell lym- phoma (DLBCL), PMBCL is now thought of as a distinct clinicopathological entity with clinical features and also a molecular signature that share similarities with
Correspondence:
JAKUB SVOBODA
jakub.svoboda@pennmedicine.upenn.edu
Received: September19,2019. Accepted: May 14, 2020. Pre-published: May 15, 2020.
https://doi.org/10.3324/haematol.2019.238675
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