Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.
Identifieur interne : 003704 ( PubMed/Corpus ); précédent : 003703; suivant : 003705Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.
Auteurs : Jesús San-Miguel ; Joan Bladé ; Ofer Shpilberg ; Sebastian Grosicki ; Frédéric Maloisel ; Chang-Ki Min ; Marta Polo Zarzuela ; Tadeusz Robak ; Sripada V S S. Prasad ; Yeow Tee Goh ; Jacob Laubach ; Andrew Spencer ; María-Victoria Mateos ; Antonio Palumbo ; Tom Puchalski ; Manjula Reddy ; Clarissa Uhlar ; Xiang Qin ; Helgi Van De Velde ; Hong Xie ; Robert Z. OrlowskiSource :
- Blood [ 1528-0020 ] ; 2014.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Antibodies, Monoclonal (administration & dosage), Antineoplastic Combined Chemotherapy Protocols (administration & dosage), Boronic Acids (administration & dosage), Bortezomib, Chromosome Deletion, Chromosomes, Human, Pair 17, Disease-Free Survival, Female, Follow-Up Studies, Humans, Immunoglobulin A (blood), Interleukin-6 (antagonists & inhibitors), Male, Melphalan (administration & dosage), Middle Aged, Multiple Myeloma (blood), Multiple Myeloma (drug therapy), Multiple Myeloma (genetics), Multiple Myeloma (mortality), Prednisone (administration & dosage), Pyrazines (administration & dosage), Survival Rate.
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Boronic Acids, Melphalan, Prednisone, Pyrazines.
- administration & dosage : Antineoplastic Combined Chemotherapy Protocols.
- chemical , antagonists & inhibitors : Interleukin-6.
- chemical , blood : Immunoglobulin A, Multiple Myeloma.
- drug therapy : Multiple Myeloma.
- genetics : Multiple Myeloma.
- mortality : Multiple Myeloma.
- Aged, Aged, 80 and over, Bortezomib, Chromosome Deletion, Chromosomes, Human, Pair 17, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Survival Rate.
Abstract
Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859.
DOI: 10.1182/blood-2013-12-546374
PubMed: 24833354
Links to Exploration step
pubmed:24833354Le document en format XML
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<author><name sortKey="San Miguel, Jesus" sort="San Miguel, Jesus" uniqKey="San Miguel J" first="Jesús" last="San-Miguel">Jesús San-Miguel</name>
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<author><name sortKey="Blade, Joan" sort="Blade, Joan" uniqKey="Blade J" first="Joan" last="Bladé">Joan Bladé</name>
<affiliation><nlm:affiliation>Institut d'Investigacions Biomediques August Pi I Sunyer, Hospital Clinic I Provincial, Barcelona, Spain;</nlm:affiliation>
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<author><name sortKey="Shpilberg, Ofer" sort="Shpilberg, Ofer" uniqKey="Shpilberg O" first="Ofer" last="Shpilberg">Ofer Shpilberg</name>
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<author><name sortKey="Grosicki, Sebastian" sort="Grosicki, Sebastian" uniqKey="Grosicki S" first="Sebastian" last="Grosicki">Sebastian Grosicki</name>
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<author><name sortKey="Min, Chang Ki" sort="Min, Chang Ki" uniqKey="Min C" first="Chang-Ki" last="Min">Chang-Ki Min</name>
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<author><name sortKey="Polo Zarzuela, Marta" sort="Polo Zarzuela, Marta" uniqKey="Polo Zarzuela M" first="Marta" last="Polo Zarzuela">Marta Polo Zarzuela</name>
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<author><name sortKey="Prasad, Sripada V S S" sort="Prasad, Sripada V S S" uniqKey="Prasad S" first="Sripada V S S" last="Prasad">Sripada V S S. Prasad</name>
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<author><name sortKey="Tee Goh, Yeow" sort="Tee Goh, Yeow" uniqKey="Tee Goh Y" first="Yeow" last="Tee Goh">Yeow Tee Goh</name>
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<author><name sortKey="Reddy, Manjula" sort="Reddy, Manjula" uniqKey="Reddy M" first="Manjula" last="Reddy">Manjula Reddy</name>
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<author><name sortKey="Qin, Xiang" sort="Qin, Xiang" uniqKey="Qin X" first="Xiang" last="Qin">Xiang Qin</name>
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<author><name sortKey="Van De Velde, Helgi" sort="Van De Velde, Helgi" uniqKey="Van De Velde H" first="Helgi" last="Van De Velde">Helgi Van De Velde</name>
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<author><name sortKey="Xie, Hong" sort="Xie, Hong" uniqKey="Xie H" first="Hong" last="Xie">Hong Xie</name>
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</affiliation>
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<author><name sortKey="Orlowski, Robert Z" sort="Orlowski, Robert Z" uniqKey="Orlowski R" first="Robert Z" last="Orlowski">Robert Z. Orlowski</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.</title>
<author><name sortKey="San Miguel, Jesus" sort="San Miguel, Jesus" uniqKey="San Miguel J" first="Jesús" last="San-Miguel">Jesús San-Miguel</name>
<affiliation><nlm:affiliation>Centro de Investigación Medica Aplicada, Clinica Universidad de Navarra, Navarra, Spain;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Blade, Joan" sort="Blade, Joan" uniqKey="Blade J" first="Joan" last="Bladé">Joan Bladé</name>
<affiliation><nlm:affiliation>Institut d'Investigacions Biomediques August Pi I Sunyer, Hospital Clinic I Provincial, Barcelona, Spain;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Shpilberg, Ofer" sort="Shpilberg, Ofer" uniqKey="Shpilberg O" first="Ofer" last="Shpilberg">Ofer Shpilberg</name>
<affiliation><nlm:affiliation>Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Grosicki, Sebastian" sort="Grosicki, Sebastian" uniqKey="Grosicki S" first="Sebastian" last="Grosicki">Sebastian Grosicki</name>
<affiliation><nlm:affiliation>Oddzial Hematologiczny SPZOZ Zespol Szpitali Miejskich w Chorzowie, Chorzow, Poland;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Maloisel, Frederic" sort="Maloisel, Frederic" uniqKey="Maloisel F" first="Frédéric" last="Maloisel">Frédéric Maloisel</name>
<affiliation><nlm:affiliation>Clinique Saint Anne, Strasbourg, France;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Min, Chang Ki" sort="Min, Chang Ki" uniqKey="Min C" first="Chang-Ki" last="Min">Chang-Ki Min</name>
<affiliation><nlm:affiliation>Seoul St. Mary's Hospital, Seoul, Republic of Korea;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Polo Zarzuela, Marta" sort="Polo Zarzuela, Marta" uniqKey="Polo Zarzuela M" first="Marta" last="Polo Zarzuela">Marta Polo Zarzuela</name>
<affiliation><nlm:affiliation>Hospital Clinico San Carlos, Madrid, Spain;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Robak, Tadeusz" sort="Robak, Tadeusz" uniqKey="Robak T" first="Tadeusz" last="Robak">Tadeusz Robak</name>
<affiliation><nlm:affiliation>Medical University of Lodz, Lodz, Poland;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prasad, Sripada V S S" sort="Prasad, Sripada V S S" uniqKey="Prasad S" first="Sripada V S S" last="Prasad">Sripada V S S. Prasad</name>
<affiliation><nlm:affiliation>Apollo Hospitals & Research Foundation, Hyderabad, India;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tee Goh, Yeow" sort="Tee Goh, Yeow" uniqKey="Tee Goh Y" first="Yeow" last="Tee Goh">Yeow Tee Goh</name>
<affiliation><nlm:affiliation>Singapore General Hospital, Singapore, Singapore;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Laubach, Jacob" sort="Laubach, Jacob" uniqKey="Laubach J" first="Jacob" last="Laubach">Jacob Laubach</name>
<affiliation><nlm:affiliation>Dana Farber Cancer Institute, Boston, MA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Spencer, Andrew" sort="Spencer, Andrew" uniqKey="Spencer A" first="Andrew" last="Spencer">Andrew Spencer</name>
<affiliation><nlm:affiliation>Alfred Health-Monash University, Melbourne, Australia;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mateos, Maria Victoria" sort="Mateos, Maria Victoria" uniqKey="Mateos M" first="María-Victoria" last="Mateos">María-Victoria Mateos</name>
<affiliation><nlm:affiliation>Hospital Universitario Salamanca, Salamanca, Spain;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Palumbo, Antonio" sort="Palumbo, Antonio" uniqKey="Palumbo A" first="Antonio" last="Palumbo">Antonio Palumbo</name>
<affiliation><nlm:affiliation>Ospedale Le Molinette, Torino, Italy;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Puchalski, Tom" sort="Puchalski, Tom" uniqKey="Puchalski T" first="Tom" last="Puchalski">Tom Puchalski</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Spring House, PA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Reddy, Manjula" sort="Reddy, Manjula" uniqKey="Reddy M" first="Manjula" last="Reddy">Manjula Reddy</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Spring House, PA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Uhlar, Clarissa" sort="Uhlar, Clarissa" uniqKey="Uhlar C" first="Clarissa" last="Uhlar">Clarissa Uhlar</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Spring House, PA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Qin, Xiang" sort="Qin, Xiang" uniqKey="Qin X" first="Xiang" last="Qin">Xiang Qin</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Spring House, PA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Van De Velde, Helgi" sort="Van De Velde, Helgi" uniqKey="Van De Velde H" first="Helgi" last="Van De Velde">Helgi Van De Velde</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Beerse, Belgium; and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Xie, Hong" sort="Xie, Hong" uniqKey="Xie H" first="Hong" last="Xie">Hong Xie</name>
<affiliation><nlm:affiliation>Janssen Research & Development, Spring House, PA;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Orlowski, Robert Z" sort="Orlowski, Robert Z" uniqKey="Orlowski R" first="Robert Z" last="Orlowski">Robert Z. Orlowski</name>
<affiliation><nlm:affiliation>The University of Texas MD Anderson Cancer Center, Houston, TX.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2014" type="published">2014</date>
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<term>Aged, 80 and over</term>
<term>Antibodies, Monoclonal (administration & dosage)</term>
<term>Antineoplastic Combined Chemotherapy Protocols (administration & dosage)</term>
<term>Boronic Acids (administration & dosage)</term>
<term>Bortezomib</term>
<term>Chromosome Deletion</term>
<term>Chromosomes, Human, Pair 17</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
<term>Immunoglobulin A (blood)</term>
<term>Interleukin-6 (antagonists & inhibitors)</term>
<term>Male</term>
<term>Melphalan (administration & dosage)</term>
<term>Middle Aged</term>
<term>Multiple Myeloma (blood)</term>
<term>Multiple Myeloma (drug therapy)</term>
<term>Multiple Myeloma (genetics)</term>
<term>Multiple Myeloma (mortality)</term>
<term>Prednisone (administration & dosage)</term>
<term>Pyrazines (administration & dosage)</term>
<term>Survival Rate</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Boronic Acids</term>
<term>Melphalan</term>
<term>Prednisone</term>
<term>Pyrazines</term>
</keywords>
<keywords scheme="MESH" qualifier="administration & dosage" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interleukin-6</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Immunoglobulin A</term>
<term>Multiple Myeloma</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Multiple Myeloma</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Multiple Myeloma</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Multiple Myeloma</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Bortezomib</term>
<term>Chromosome Deletion</term>
<term>Chromosomes, Human, Pair 17</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
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<front><div type="abstract" xml:lang="en">Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24833354</PMID>
<DateCreated><Year>2014</Year>
<Month>06</Month>
<Day>27</Day>
</DateCreated>
<DateCompleted><Year>2014</Year>
<Month>09</Month>
<Day>04</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>11</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1528-0020</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>123</Volume>
<Issue>26</Issue>
<PubDate><Year>2014</Year>
<Month>Jun</Month>
<Day>26</Day>
</PubDate>
</JournalIssue>
<Title>Blood</Title>
<ISOAbbreviation>Blood</ISOAbbreviation>
</Journal>
<ArticleTitle>Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.</ArticleTitle>
<Pagination><MedlinePgn>4136-42</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1182/blood-2013-12-546374</ELocationID>
<Abstract><AbstractText>Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859.</AbstractText>
<CopyrightInformation>© 2014 by The American Society of Hematology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>San-Miguel</LastName>
<ForeName>Jesús</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Centro de Investigación Medica Aplicada, Clinica Universidad de Navarra, Navarra, Spain;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bladé</LastName>
<ForeName>Joan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institut d'Investigacions Biomediques August Pi I Sunyer, Hospital Clinic I Provincial, Barcelona, Spain;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shpilberg</LastName>
<ForeName>Ofer</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Grosicki</LastName>
<ForeName>Sebastian</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Oddzial Hematologiczny SPZOZ Zespol Szpitali Miejskich w Chorzowie, Chorzow, Poland;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Maloisel</LastName>
<ForeName>Frédéric</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Clinique Saint Anne, Strasbourg, France;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Min</LastName>
<ForeName>Chang-Ki</ForeName>
<Initials>CK</Initials>
<AffiliationInfo><Affiliation>Seoul St. Mary's Hospital, Seoul, Republic of Korea;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Polo Zarzuela</LastName>
<ForeName>Marta</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Hospital Clinico San Carlos, Madrid, Spain;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Robak</LastName>
<ForeName>Tadeusz</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Medical University of Lodz, Lodz, Poland;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Prasad</LastName>
<ForeName>Sripada V S S</ForeName>
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<Initials>RZ</Initials>
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<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
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<MeshHeading><DescriptorName UI="D008558" MajorTopicYN="N">Melphalan</DescriptorName>
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<MeshHeading><DescriptorName UI="D009101" MajorTopicYN="N">Multiple Myeloma</DescriptorName>
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