Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma : A multicenter phase II study
Identifieur interne : 00CB05 ( Main/Exploration ); précédent : 00CB04; suivant : 00CB06Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma : A multicenter phase II study
Auteurs : B. Coiffier [France, Allemagne, Australie, Royaume-Uni, Suisse] ; C. Haioun ; N. Ketterer ; A. Engert ; H. Tilly ; D. Ma ; P. Johnson ; A. Lister ; M. F.- Buske ; J. A. Radford ; R. Capdeville ; V. Diehl ; F. ReyesSource :
- Blood [ 0006-4971 ] ; 1998.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Rituximab, a chimeric monoclonal antibody that binds specifically to the CD20 antigen, induced objective responses in 50% of patients with low-grade or follicular B-cell lymphoma. Because most nonfollicular B-cell lymphomas also express the CD20 antigen, we conducted a phase II study to evaluate the efficacy and tolerability of this new agent in patients with more aggressive types of lymphoma. Patients with diffuse large B-cell lymphoma (DLCL), mantle cell lymphoma (MCL), or other intermediate- or high-grade B-cell lymphomas according to the Working Formulation were included in this prospective randomized phase II study if they were in first or second relapse, if they were refractory to initial therapy, if they progressed after a partial response to initial therapy, or if they were elderly (age > 60 years) and not previously treated. The patients received 8 weekly infusions of rituximab at the dose of 375 mg/m2 in arm A or one infusion of 375 mg/m2 followed by 7 weekly infusions of 500 mg/m2 in arm B. Patients were evaluated 2 months after the last rituximab infusion. Fifty-four patients were randomized from 9 centers in Europe and Australia (28 in arm A and 26 in arm B). A total of 5 complete responses (CR) and 12 partial responses (PR) were observed among the 54 enrolled patients, with no difference between the two doses. In an intent-to-treat analysis, the CR rate was 9% (Cl95%, 3% to 20%) and the PR rate was 22% (Cl95%, 12% to 36%), for an overall response rate of 31% (Cl95%, 20% to 46%). An analysis of prognostic factors showed that response rates were lower in patients with refractory disease, patients with lymphoma not classified as DLCL, and patients with a tumor larger than 5 cm in diameter. DLCL and MCL patients had response rates of 37% and 33%, respectively. The median time to progression exceeded 246 days for the 17 responding patients. The most frequently reported adverse events were related to an infusion syndrome and were mild: 19% of the patients had a grade 3 related adverse event, slightly more in arm B, and only 1 patient had a grade 4 related adverse event in arm A. Two patients (3.7%) withdrew from treatment because of severe adverse events, one patient in each arm. In this first trial of rituximab in DLCL and MCL, patients experienced a significant clinical activity with a low toxicity. Rituximab has significant activity in DLCL and MCL patients and should be tested in combination with chemotherapy in such patients.
Affiliations:
- Allemagne, Australie, France, Royaume-Uni, Suisse
- Angleterre, Basse-Saxe, District de Cologne, Grand Londres, Grand Manchester, Haute-Normandie, Rhénanie-du-Nord-Westphalie, Région Normandie, Île-de-France
- Cologne, Créteil, Göttingen, Londres, Manchester, Rouen
- Université de Manchester
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Le document en format XML
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Reyes</name></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">98-0453928</idno><date when="1998">1998</date><idno type="stanalyst">PASCAL 98-0453928 INIST</idno><idno type="RBID">Pascal:98-0453928</idno><idno type="wicri:Area/PascalFrancis/Corpus">006592</idno><idno type="wicri:Area/PascalFrancis/Curation">006A70</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">006276</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">006276</idno><idno type="wicri:doubleKey">0006-4971:1998:Coiffier B:rituximab:anti:cd</idno><idno type="wicri:Area/Main/Merge">00DB63</idno><idno type="wicri:Area/Main/Curation">00CB05</idno><idno type="wicri:Area/Main/Exploration">00CB05</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma : A multicenter phase II study</title><author><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Service d'Hématologie, Centre Hospitalier Lyon-Sud</s1><s2>Pierre-Bénite</s2><s3>FRA</s3></inist:fA14><country>France</country><wicri:noRegion>Pierre-Bénite</wicri:noRegion><wicri:noRegion>Centre Hospitalier Lyon-Sud</wicri:noRegion><wicri:noRegion>Pierre-Bénite</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Service d'Hématologie, Hôpital Henri-Mondor</s1><s2>Créteil</s2><s3>FRA</s3></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Klinik 1 fur Innere Medezin, Üniversität zu Köln</s1><s2>Köln</s2><s3>DEU</s3></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Service d'Hématologie, Centre Henri Bécquerel</s1><s2>Rouen</s2><s3>FRA</s3></inist:fA14><country>France</country><placeName><region type="region">Région Normandie</region><region type="old region">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Hematolgy, Royal North Shore Hospital</s1><s2>St Leonards</s2><s3>AUS</s3></inist:fA14><country>Australie</country><wicri:noRegion>St Leonards</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Cancer Research Building, St James University Hospital</s1><s2>Leeds</s2><s3>GBR</s3></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Leeds</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Medical Oncology, St Bartholomew's Hospital</s1><s2>London</s2><s3>GBR</s3></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Zentrum fur Innere Medizin, Abt. Hematologie und Onkologie, August Universität</s1><s2>Göttingen</s2><s3>DEU</s3></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="09"><s1>CRC Department of Medical Oncology, University of Manchester</s1><s2>Manchester</s2><s3>GBR</s3></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region><settlement type="city">Manchester</settlement></placeName><orgName type="university">Université de Manchester</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Hoffman-La Roche</s1><s2>Basel</s2><s3>CHE</s3></inist:fA14><country>Suisse</country><wicri:noRegion>Hoffman-La Roche</wicri:noRegion></affiliation></author><author><name sortKey="Haioun, C" sort="Haioun, C" uniqKey="Haioun C" first="C." last="Haioun">C. Haioun</name></author><author><name sortKey="Ketterer, N" sort="Ketterer, N" uniqKey="Ketterer N" first="N." last="Ketterer">N. Ketterer</name></author><author><name sortKey="Engert, A" sort="Engert, A" uniqKey="Engert A" first="A." last="Engert">A. Engert</name></author><author><name sortKey="Tilly, H" sort="Tilly, H" uniqKey="Tilly H" first="H." last="Tilly">H. Tilly</name></author><author><name sortKey="Ma, D" sort="Ma, D" uniqKey="Ma D" first="D." last="Ma">D. Ma</name></author><author><name sortKey="Johnson, P" sort="Johnson, P" uniqKey="Johnson P" first="P." last="Johnson">P. Johnson</name></author><author><name sortKey="Lister, A" sort="Lister, A" uniqKey="Lister A" first="A." last="Lister">A. Lister</name></author><author><name sortKey="Buske, M F" sort="Buske, M F" uniqKey="Buske M" first="M. F.-" last="Buske">M. F.- Buske</name></author><author><name sortKey="Radford, J A" sort="Radford, J A" uniqKey="Radford J" first="J. A." last="Radford">J. A. Radford</name></author><author><name sortKey="Capdeville, R" sort="Capdeville, R" uniqKey="Capdeville R" first="R." last="Capdeville">R. Capdeville</name></author><author><name sortKey="Diehl, V" sort="Diehl, V" uniqKey="Diehl V" first="V." last="Diehl">V. Diehl</name></author><author><name sortKey="Reyes, F" sort="Reyes, F" uniqKey="Reyes F" first="F." last="Reyes">F. Reyes</name></author></analytic><series><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno><imprint><date when="1998">1998</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>B-Lymphocyte</term><term>Human</term><term>Immunotherapy</term><term>Monoclonal antibody</term><term>Multicenter study</term><term>Negative therapeutic reaction</term><term>Non Hodgkin lymphoma</term><term>Phase II trial</term><term>Recurrent</term><term>Rituximab</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Lymphome non hodgkinien</term><term>Lymphocyte B</term><term>Récidivant</term><term>Anticorps monoclonal</term><term>Résistance traitement</term><term>Rituximab</term><term>Immunothérapie</term><term>Traitement</term><term>Essai clinique phase II</term><term>Etude multicentrique</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Rituximab, a chimeric monoclonal antibody that binds specifically to the CD20 antigen, induced objective responses in 50% of patients with low-grade or follicular B-cell lymphoma. Because most nonfollicular B-cell lymphomas also express the CD20 antigen, we conducted a phase II study to evaluate the efficacy and tolerability of this new agent in patients with more aggressive types of lymphoma. Patients with diffuse large B-cell lymphoma (DLCL), mantle cell lymphoma (MCL), or other intermediate- or high-grade B-cell lymphomas according to the Working Formulation were included in this prospective randomized phase II study if they were in first or second relapse, if they were refractory to initial therapy, if they progressed after a partial response to initial therapy, or if they were elderly (age > 60 years) and not previously treated. The patients received 8 weekly infusions of rituximab at the dose of 375 mg/m<sup>2</sup> in arm A or one infusion of 375 mg/m<sup>2</sup> followed by 7 weekly infusions of 500 mg/m<sup>2</sup> in arm B. Patients were evaluated 2 months after the last rituximab infusion. Fifty-four patients were randomized from 9 centers in Europe and Australia (28 in arm A and 26 in arm B). A total of 5 complete responses (CR) and 12 partial responses (PR) were observed among the 54 enrolled patients, with no difference between the two doses. In an intent-to-treat analysis, the CR rate was 9% (Cl<sub>95%</sub>, 3% to 20%) and the PR rate was 22% (Cl<sub>95%</sub>, 12% to 36%), for an overall response rate of 31% (Cl<sub>95%</sub>, 20% to 46%). An analysis of prognostic factors showed that response rates were lower in patients with refractory disease, patients with lymphoma not classified as DLCL, and patients with a tumor larger than 5 cm in diameter. DLCL and MCL patients had response rates of 37% and 33%, respectively. The median time to progression exceeded 246 days for the 17 responding patients. The most frequently reported adverse events were related to an infusion syndrome and were mild: 19% of the patients had a grade 3 related adverse event, slightly more in arm B, and only 1 patient had a grade 4 related adverse event in arm A. Two patients (3.7%) withdrew from treatment because of severe adverse events, one patient in each arm. In this first trial of rituximab in DLCL and MCL, patients experienced a significant clinical activity with a low toxicity. Rituximab has significant activity in DLCL and MCL patients and should be tested in combination with chemotherapy in such patients.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Angleterre</li><li>Basse-Saxe</li><li>District de Cologne</li><li>Grand Londres</li><li>Grand Manchester</li><li>Haute-Normandie</li><li>Rhénanie-du-Nord-Westphalie</li><li>Région Normandie</li><li>Île-de-France</li></region><settlement><li>Cologne</li><li>Créteil</li><li>Göttingen</li><li>Londres</li><li>Manchester</li><li>Rouen</li></settlement><orgName><li>Université de Manchester</li></orgName></list><tree><noCountry><name sortKey="Buske, M F" sort="Buske, M F" uniqKey="Buske M" first="M. F.-" last="Buske">M. F.- Buske</name><name sortKey="Capdeville, R" sort="Capdeville, R" uniqKey="Capdeville R" first="R." last="Capdeville">R. Capdeville</name><name sortKey="Diehl, V" sort="Diehl, V" uniqKey="Diehl V" first="V." last="Diehl">V. Diehl</name><name sortKey="Engert, A" sort="Engert, A" uniqKey="Engert A" first="A." last="Engert">A. Engert</name><name sortKey="Haioun, C" sort="Haioun, C" uniqKey="Haioun C" first="C." last="Haioun">C. Haioun</name><name sortKey="Johnson, P" sort="Johnson, P" uniqKey="Johnson P" first="P." last="Johnson">P. Johnson</name><name sortKey="Ketterer, N" sort="Ketterer, N" uniqKey="Ketterer N" first="N." last="Ketterer">N. Ketterer</name><name sortKey="Lister, A" sort="Lister, A" uniqKey="Lister A" first="A." last="Lister">A. Lister</name><name sortKey="Ma, D" sort="Ma, D" uniqKey="Ma D" first="D." last="Ma">D. Ma</name><name sortKey="Radford, J A" sort="Radford, J A" uniqKey="Radford J" first="J. A." last="Radford">J. A. Radford</name><name sortKey="Reyes, F" sort="Reyes, F" uniqKey="Reyes F" first="F." last="Reyes">F. Reyes</name><name sortKey="Tilly, H" sort="Tilly, H" uniqKey="Tilly H" first="H." last="Tilly">H. Tilly</name></noCountry><country name="France"><noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></region><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></country><country name="Australie"><noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></country><country name="Suisse"><noRegion><name sortKey="Coiffier, B" sort="Coiffier, B" uniqKey="Coiffier B" first="B." last="Coiffier">B. Coiffier</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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