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Review
. 2020 Jun 23:13:5993-6009.
doi: 10.2147/OTT.S193951. eCollection 2020.

Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma

Shinichi Makita  1 , Dai Maruyama  1 , Kensei Tobinai  1
Affiliations
Review

Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma

Shinichi Makita et al. Onco Targets Ther. .

Abstract

Classical Hodgkin lymphoma (cHL) is a B-cell-derived lymphoid malignancy with the most favorable prognosis among various adult malignancies. However, once it becomes refractory disease to chemotherapy or relapses after high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT), it is difficult to manage with conventional cytotoxic chemotherapy. The introduction of brentuximab vedotin (BV) has changed the treatment landscape of cHL in the past decade. Several studies demonstrated high efficacy of BV monotherapy in heavily treated patients with cHL relapsed or refractory after HDC/ASCT. Recent studies also reported high efficacy of concurrent or sequential combination of BV and chemotherapy in patients with transplant-eligible relapsed/refractory cHL at the second-line setting. In addition, a randomized phase III trial ECHELON-1 reported a positive result of BV in combination with AVD (doxorubicin, vinblastine, and dacarbazine) in patients with newly diagnosed advanced-stage cHL. In this review, we summarize available data of BV for cHL and discuss the current and future role of BV in the management of cHL.

Keywords: CD30; MMAE; antibody-drug conjugate; brentuximab vedotin; classic Hodgkin lymphoma.

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Conflict of interest statement

SM received honoraria from Takeda, Novartis, Eisai, and Celgene. DM received honoraria from Ono Pharmaceutical, Celgene, Takeda, Janssen, Eisai, Chugai Pharma, Kyowa Hakko Kirin, Zenyaku Kogyo, Bristol-Myers Squibb, Synmosa Biopharma Corporation, Nippon Shinyaku, and research funding from Merck, Amgen Astellas BioPharma, Astellas Pharma, Sanofi, Celgene, Novartis Pharma, Bristol-Myers Squibb, Janssen, Ono Pharmaceutical, Otsuka, Chugai Pharma, and Takeda. KT received honoraria from Zenyaku Kogyo, Eisai, Takeda, Mundipharma, HUYA Bioscience International, Kyowa Hakko Kirin, Celgene, Chugai Pharma, Ono Pharmaceutical, Yakult, Daiichi Sankyo, Bristol-Meyers Squibb, Meiji Seika Kaisha, Solacia Pharma, Verastem, and serving consulting or advisory role in Celgene, Zenyaku Kogyo, Huya Bioscience, Daiichi Sankyo, Takeda, Mundipharma, Ono Pharmaceutical, and received research funding from Chugai Pharma, Kyowa Hakko Kirin, Ono Pharmaceutical, Celgene, Janssen, Eisai, Mundi Pharma, Takeda, and Abbvie. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Brentuximab vedotin (BV). BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody and the microtubule-disrupting agent monomethyl auristatin E (MMAE) (A). BV binds to CD30 expressed on the surface of lymphoma cells and is internalized via endocytosis. The cytoplasmic lysosomal enzymes decompose the linker protein that conjugates the CD30 antibody and MMAE. The MMAE released to the cytoplasm inhibits the synthesis of microtubules and leads to apoptosis of lymphoma cells (B).
Figure 2
Figure 2
Example of sequential combination of BV and salvage chemotherapy: Weekly BV followed by augmented ICE. Abbreviations: BV, brentuximab vedotin; HDC/ASCT, high-dose chemotherapy with autologous stem cell transplantation; ICE, ifosfamide, carboplatin, and etoposide; PET, positron emission tomography.
Figure 3
Figure 3
Example of concurrent combination of BV and salvage chemotherapy: BRESHAP. Abbreviations: BV, brentuximab vedotin; ESHAP, etoposide, methylprednisolone, cytarabine, and cisplatin; HDC/ASCT, high-dose chemotherapy with autologous stem cell transplantation; PBSC, peripheral blood stem cell.
Figure 4
Figure 4
Current treatment strategy for untreated classic Hodgkin lymphoma. Abbreviations: ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; AVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; BV brentuximab vedotin; IFRT, involved-field radiotherapy; PET-CT, positron emission tomography-computed tomography.
Figure 5
Figure 5
Current treatment strategy for relapsed/refractory classic Hodgkin lymphoma. Abbreviations: BV, brentuximab vedotin; CR, complete response; HDC/ASCT, high-dose chemotherapy with autologous stem cell transplantation; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 6
Figure 6
Signaling pathways and genomic alterations in Hodgkin Reed Sternberg cell Activating mutations are highlighted in red, and loss-of-function mutations are highlighted in gray. Abbreviations: B2M, beta-2 microglobulin; CIITA, class II major histocompatibility complex transactivator; ERK, extracellular signal-regulated kinase; HLA, major histocompatibility complex; IKK, I kappa kinase; JAK, Janus kinase; LMP1, latent membrane protein 1; MAPK, mitogen-activated protein kinase; mTORC1, mammalian target of rapamycin complex 1; NEMO, NF-κB essential modulator; NF-κB, nuclear factor kappa B; NIK, NF-κB-inducing kinase; PDCD1LG2, programmed cell death 1 ligand 2; PD-L1/-L2, programmed cell death-ligand 1/-ligand 2; PI3K, phosphatidylinositol 3-kinase; PTP1B, protein tyrosine phosphatase 1B; RANK, receptor activator of nuclear factor kappa B; RIP, receptor interacting protein; Rheb, Ras homolog enriched in brain; SOCS, suppressor of cytokine signaling; STAT, signal transducers and activator of transcription; TRAF, TNF receptor associated factor.
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