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RF - Brentuximab as Treatment for CD30+ Primary Cutaneous Lymphoma
FR - Brentuximab como tratamiento de los linfomas cutáneos primarios CD30
D. Morgado-Carrasco, A. Combalia, T. Estrach Panella
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Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España
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Morgado-Carrasco, A. Combalia, T. Estrach Panella" "autores" => array:3 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Combalia" ] 2 => array:4 [ "nombre" => "T." "apellidos" => "Estrach Panella" "email" => array:1 [ 0 => "testrach@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "FR - Brentuximab como tratamiento de los linfomas cutáneos primarios CD30" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Mycosis fungoides and cutaneous anaplastic large-cell lymphoma (CALCL) are primary T-cell lymphomas. Prognosis is good in the initial stages, and the wide range of available first-line treatments includes topical corticosteroids, phototherapy, localized radiotherapy, and mechlorethamine. Survival is lower and quality of life considerably affected in advanced stages. The recommended treatment options include bexarotene, methotrexate, interferon, chemotherapy, and radiotherapy.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Brentuximab is a monoclonal antibody that targets CD30 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). It is approved by the United States Food and Drug Administration (FDA) for the treatment of Hodgkin lymphoma that is refractory to chemotherapy and autologous hematopoietic stem cell transplant and for the treatment of refractory anaplastic large-cell lymphoma.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The FDA recently approved its use in mycosis fungoides with expression of CD30 (MF-CD30<span class="elsevierStyleSup">+</span>) and in CALCL-CD30<span class="elsevierStyleSup">+</span> based on the results of a phase 3 multicenter randomized clinical trial, ALCANZA,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> which included 131 patients with MF-CD30<span class="elsevierStyleSup">+</span> (n = 97), CD30 expression ><span class="elsevierStyleHsp" style=""></span>10%, or CALCL (n = 31) who had previously been treated with systemic agents or radiotherapy. The intention-to-treat analysis included 128 individuals (3 were excluded because of CD30 expression <<span class="elsevierStyleHsp" style=""></span>10%). Of these, 64 received brentuximab (16 cycles of 1.8<span class="elsevierStyleHsp" style=""></span>mg/kg every 3 wk) and 64 received therapy chosen by the attending physician (physician's choice) with oral bexarotene (300<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/d) or methotrexate (5-50<span class="elsevierStyleHsp" style=""></span>mg/wk) for up to 48 weeks. The primary endpoint was the percentage of patients achieving an objective global response lasting at least 4 months. After a mean follow-up of almost 2 years (22.9<span class="elsevierStyleHsp" style=""></span>mo), the objective overall response at 4 months was 56.3% in the brentuximab group compared with 12.5% in the physician's choice group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0001). Complete response was 16% in the brentuximab group compared with 2% in the physician's choice group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0046). Progression-free survival was also higher with brentuximab (16.7 vs 3.5<span class="elsevierStyleHsp" style=""></span>mo in the physician's choice group), as was symptom relief. The outcome of treatment with brentuximab was better than that of bexarotene or methotrexate, irrespective of age, sex, type of cutaneous T-cell lymphoma (MF-CD30<span class="elsevierStyleSup">+</span> or CALCL), and involvement (cutaneous vs visceral-cutaneous).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The frequency of adverse events was 29% in both groups. In the brentuximab group, 24% of patients had to suspend treatment because of adverse events compared with 8% in the physician's choice group. Peripheral neuropathy was the most frequent toxicity (67%) with brentuximab. Symptoms improved during posttreatment follow-up in 82% of those affected.</p><p id="par0020" class="elsevierStylePara elsevierViewall">CD30 expression is variable in mycosis fungoides, and there is no consensus on the minimum threshold necessary to obtain a clinical response with brentuximab. A phase 2 study with this agent revealed clinical responses even with CD30 expression <<span class="elsevierStyleHsp" style=""></span>5% (response rate of 17%), although greater response rates (up to 83%) were observed in those cases of mycosis fungoides with expression ><span class="elsevierStyleHsp" style=""></span>5%.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> In another phase 2 study, Duvic et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> found no differences in response between patients with low expression (<<span class="elsevierStyleHsp" style=""></span>10%) and high expression of CD30. In a recent report, a patient with CD30-negative mycosis fungoides (CD30 <<span class="elsevierStyleHsp" style=""></span>1%) that was refractory to multiple treatment lines achieved a complete response with brentuximab.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">As for dosing, a recent systematic review showed that lower doses of brentuximab (1.2<span class="elsevierStyleHsp" style=""></span>mg/kg every 3 wk) could be equally effective, with fewer adverse effects.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Brentuximab has proven to be superior to habitual treatments for advanced phase CD30-positive cutaneous large-cell lymphoma, although questions remain concerning the minimum threshold of CD30 expression for the therapy to be considered effective. Dermatologists should make every effort to become familiar with the growing list of currently available biologics. We believe that this new alternative therapy will prolong the survival of patients with advanced CD30-positive cutaneous T-cell lymphoma, although its high cost is a major limitation to its use.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1174191" "palabras" => array:4 [ 0 => "Brentuximab" 1 => "Micosis fungoides" 2 => "Primary cutaneous anaplastic large cell lymphoma" 3 => "Cutaneous lymphoma" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morgado-Carrasco D, Combalia A, Estrach Panella T. FR - Brentuximab como tratamiento de los linfomas cutáneos primarios CD30 Eczema y urticaria en Portugal. 2019;110:769–770.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Source: Scott et al.,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Prince et al..<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Type of Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Target \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Mechanism of Action \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Route of Administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Frequent Adverse Effects \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conjugate formed by a monoclonal antibody covalently bound to monomethyl auristatin E. Covalent binding is via a dipeptide sensitive to degradation by liposomal proteases. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD30 antigen, a 120-kD transmembrane protein belonging to the tumor necrosis factor receptor superfamily \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Internalization of the drug by CD30<span class="elsevierStyleSup">+</span> cells is accompanied by release of monomethyl auristatin E. This cytotoxic agent inhibits polymerization of the microtubules, stops the cell cycle, and causes cell apoptosis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intravenous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral sensory neuropathy, nausea, diarrhea, vomiting, asthenia, alopecia, pruritus, fever, neutropenia, upper respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2169907.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Brentuximab.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2017" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 4 | 8 | 12 |
| 2024 Octubre | 83 | 50 | 133 |
| 2024 Septiembre | 77 | 26 | 103 |
| 2024 Agosto | 96 | 72 | 168 |
| 2024 Julio | 86 | 29 | 115 |
| 2024 Junio | 93 | 42 | 135 |
| 2024 Mayo | 85 | 32 | 117 |
| 2024 Abril | 86 | 22 | 108 |
| 2024 Marzo | 80 | 34 | 114 |
| 2024 Febrero | 76 | 31 | 107 |
| 2024 Enero | 74 | 34 | 108 |
| 2023 Diciembre | 69 | 18 | 87 |
| 2023 Noviembre | 72 | 30 | 102 |
| 2023 Octubre | 73 | 27 | 100 |
| 2023 Septiembre | 54 | 29 | 83 |
| 2023 Agosto | 57 | 17 | 74 |
| 2023 Julio | 74 | 41 | 115 |
| 2023 Junio | 62 | 24 | 86 |
| 2023 Mayo | 47 | 19 | 66 |
| 2023 Abril | 41 | 21 | 62 |
| 2023 Marzo | 59 | 25 | 84 |
| 2023 Febrero | 55 | 18 | 73 |
| 2023 Enero | 31 | 36 | 67 |
| 2022 Diciembre | 55 | 46 | 101 |
| 2022 Noviembre | 53 | 35 | 88 |
| 2022 Octubre | 41 | 33 | 74 |
| 2022 Septiembre | 72 | 38 | 110 |
| 2022 Agosto | 77 | 45 | 122 |
| 2022 Julio | 58 | 37 | 95 |
| 2022 Junio | 42 | 43 | 85 |
| 2022 Mayo | 49 | 47 | 96 |
| 2022 Abril | 67 | 27 | 94 |
| 2022 Marzo | 96 | 59 | 155 |
| 2022 Febrero | 64 | 21 | 85 |
| 2022 Enero | 66 | 33 | 99 |
| 2021 Diciembre | 63 | 37 | 100 |
| 2021 Noviembre | 51 | 41 | 92 |
| 2021 Octubre | 59 | 49 | 108 |
| 2021 Septiembre | 50 | 41 | 91 |
| 2021 Agosto | 50 | 29 | 79 |
| 2021 Julio | 38 | 19 | 57 |
| 2021 Junio | 85 | 28 | 113 |
| 2021 Mayo | 83 | 43 | 126 |
| 2021 Abril | 103 | 73 | 176 |
| 2021 Marzo | 54 | 32 | 86 |
| 2021 Febrero | 57 | 19 | 76 |
| 2021 Enero | 32 | 18 | 50 |
| 2020 Diciembre | 29 | 14 | 43 |
| 2020 Noviembre | 23 | 10 | 33 |
| 2020 Octubre | 30 | 10 | 40 |
| 2020 Septiembre | 35 | 17 | 52 |
| 2020 Agosto | 26 | 18 | 44 |
| 2020 Julio | 15 | 18 | 33 |
| 2020 Junio | 19 | 28 | 47 |
| 2020 Mayo | 17 | 13 | 30 |
| 2020 Abril | 15 | 9 | 24 |
| 2020 Marzo | 10 | 4 | 14 |
| 2020 Febrero | 3 | 2 | 5 |
| 2019 Septiembre | 1 | 2 | 3 |
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