Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial
Summary Background Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to stud...
Gespeichert in:
| Veröffentlicht in: | The Lancet (British edition) 2017-02, Vol.389 (10068), p.519-527 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 527 |
|---|---|
| container_issue | 10068 |
| container_start_page | 519 |
| container_title | The Lancet (British edition) |
| container_volume | 389 |
| creator | Durie, Brian G M, Dr Prof Hoering, Antje, PhD Abidi, Muneer H, MD Rajkumar, S Vincent, Prof Epstein, Joshua, Prof Kahanic, Stephen P, MD Thakuri, Mohan, MD Reu, Frederic, MD Reynolds, Christopher M, MD Sexton, Rachael, MS Orlowski, Robert Z, Prof Barlogie, Bart, Prof Dispenzieri, Angela, Prof |
| description | Summary Background Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. Methods In this randomised, open-label, phase 3 trial, we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group (SWOG) and National Clinical Trial Network (NCTN) institutions (both inpatient and outpatient settings). Key inclusion criteria were presence of CRAB (C=calcium elevation; R=renal impairment; A=anaemia; B=bone involvement) criteria with measurable disease (measured by assessment of free light chains), Eastern Cooperative Oncology Group (ECOG) performance status of 0–3, haemoglobin concentration 9 g/dL or higher, absolute neutrophil count 1 × 103 cells per mm3 or higher, and a platelet count of 80 000/mm3 or higher. We randomly assigned (1:1) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone (VRd group) or lenalidomide and dexamethasone alone (Rd group). Randomisation was stratified based on International Staging System stage (I, II, or III) and intent to transplant (yes vs no). The VRd regimen was given as eight 21-day cycles. Bortezomib was given at 1·3 mg/m2 intravenously on days 1, 4, 8, and 11, combined with oral lenalidomide 25 mg daily on days 1–14 plus oral dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12. The Rd regimen was given as six 28-day cycles. The standard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1–21 plus 40 mg oral dexamethasone once a day on days 1, 8, 15, and 22. The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02. Analyses were intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00644228. Findings Between April, 2008, and February, 2012, we randomly assigned 525 patients at 139 participating institutions (264 to VRd and 261 to Rd). In the randomly assigned patients, 21 patients in the VRd group and |
| doi_str_mv | 10.1016/S0140-6736(16)31594-X |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5546834</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S014067361631594X</els_id><sourcerecordid>2317867427</sourcerecordid><originalsourceid>FETCH-LOGICAL-c630t-8fe4b1226156acf0b16253e1c8bed4a9bca9d7dd965ecdd94c1ea869938781dd3</originalsourceid><addsrcrecordid>eNqFksFuEzEQhlcIREPgEUCWuKRSF-y117vhUAQVFKRKPRREbpbXnjQu3nWwnZbw4JyZJKVAD_Riy55vfs-M_6J4yugLRpl8eUaZoKVsuJwwuc9ZPRXl7F4xYqIRZS2a2f1idIPsFY9SuqCUCknrh8Ve1VLWCCpHxc-3IWb4EXrXkSuXF8TDoL2zeGGB6MESC991D3mhUxiAXEJMq3QXpf1mdQNZ6uxgyGmnPcCVXxPr9PkQEljSr8GHXm-DYZUxISNM5iES1_eAYEatVQ4-nAd8NWXoSwPekxz1kJZeIz05-3J6TM5o0zT7r4gmGNnUhfoHJCxhKL3uwB-QJdYGhGOq0_5x8WCufYIn1_u4-Pz-3aejD-XJ6fHHozcnpZGc5rKdg-hYVUlWS23mtGOyqjkw03ZghZ52Rk9tY-1U1mBwE4aBbuV0ytumZdbycXG4012uOmzIYHtRe7WMrtdxrYJ26t_I4BbqPFyquhay5QIFJtcCMXxbQcoKW9uMQA-AI1GsrTmvK47wuHh-C70Iq4j_lFTFWdPKRlTN_yjWSlTCOTKk6h1lYkgpwvymZEbVxn9q6z-1MZfC09Z_aoZ5z_7u9ybrt-EQeL0DAKd-6SCqZNAhBj87gsnKBnfnE4e3FIx3gzPaf4U1pD_dqFQpuhPZaDC5VZjxX96hBlg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1865237771</pqid></control><display><type>article</type><title>Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Durie, Brian G M, Dr Prof ; Hoering, Antje, PhD ; Abidi, Muneer H, MD ; Rajkumar, S Vincent, Prof ; Epstein, Joshua, Prof ; Kahanic, Stephen P, MD ; Thakuri, Mohan, MD ; Reu, Frederic, MD ; Reynolds, Christopher M, MD ; Sexton, Rachael, MS ; Orlowski, Robert Z, Prof ; Barlogie, Bart, Prof ; Dispenzieri, Angela, Prof</creator><creatorcontrib>Durie, Brian G M, Dr Prof ; Hoering, Antje, PhD ; Abidi, Muneer H, MD ; Rajkumar, S Vincent, Prof ; Epstein, Joshua, Prof ; Kahanic, Stephen P, MD ; Thakuri, Mohan, MD ; Reu, Frederic, MD ; Reynolds, Christopher M, MD ; Sexton, Rachael, MS ; Orlowski, Robert Z, Prof ; Barlogie, Bart, Prof ; Dispenzieri, Angela, Prof</creatorcontrib><description>Summary Background Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. Methods In this randomised, open-label, phase 3 trial, we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group (SWOG) and National Clinical Trial Network (NCTN) institutions (both inpatient and outpatient settings). Key inclusion criteria were presence of CRAB (C=calcium elevation; R=renal impairment; A=anaemia; B=bone involvement) criteria with measurable disease (measured by assessment of free light chains), Eastern Cooperative Oncology Group (ECOG) performance status of 0–3, haemoglobin concentration 9 g/dL or higher, absolute neutrophil count 1 × 103 cells per mm3 or higher, and a platelet count of 80 000/mm3 or higher. We randomly assigned (1:1) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone (VRd group) or lenalidomide and dexamethasone alone (Rd group). Randomisation was stratified based on International Staging System stage (I, II, or III) and intent to transplant (yes vs no). The VRd regimen was given as eight 21-day cycles. Bortezomib was given at 1·3 mg/m2 intravenously on days 1, 4, 8, and 11, combined with oral lenalidomide 25 mg daily on days 1–14 plus oral dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12. The Rd regimen was given as six 28-day cycles. The standard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1–21 plus 40 mg oral dexamethasone once a day on days 1, 8, 15, and 22. The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02. Analyses were intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00644228. Findings Between April, 2008, and February, 2012, we randomly assigned 525 patients at 139 participating institutions (264 to VRd and 261 to Rd). In the randomly assigned patients, 21 patients in the VRd group and 31 in the Rd group were deemed ineligible based mainly on missing, insufficient, or early or late baseline laboratory data. Median progression-free survival was significantly improved in the VRd group (43 months vs 30 months in the Rd group; stratified hazard ratio [HR] 0·712, 96% CI 0·56–0·906; one-sided p value 0·0018). The median overall survival was also significantly improved in the VRd group (75 months vs 64 months in the Rd group, HR 0·709, 95% CI 0·524–0·959; two-sided p value 0·025). The rates of overall response (partial response or better) were 82% (176/216) in the VRd group and 72% (153/214) in the Rd group, and 16% (34/216) and 8% (18/214) of patients who were assessable for response in these respective groups had a complete response or better. Adverse events of grade 3 or higher were reported in 198 (82%) of 241 patients in the VRd group and 169 (75%) of 226 patients in the Rd group; 55 (23%) and 22 (10%) patients discontinued induction treatment because of adverse events, respectively. There were no treatment-related deaths in the Rd group, and two in the VRd group. Interpretation In patients with newly diagnosed myeloma, the addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile. Funding NIH, NCI, NCTN, Millennium Pharmaceuticals, Takeda Oncology Company, and Celgene Corporation.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(16)31594-X</identifier><identifier>PMID: 28017406</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Anemia ; Angiogenesis Inhibitors - therapeutic use ; Antineoplastic Agents - therapeutic use ; Autografts ; Bortezomib ; Bortezomib - therapeutic use ; Calcium ; Clinical trials ; Dexamethasone ; Dexamethasone - therapeutic use ; Disease-Free Survival ; Drug dosages ; Drug therapy ; Drug Therapy, Combination ; Female ; Hematology ; Hematopoietic Stem Cell Transplantation ; Hemoglobin ; Humans ; Immunotherapy ; Inhibitor drugs ; Internal Medicine ; Lenalidomide ; Light chains ; Male ; Medical diagnosis ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - drug therapy ; Multiple Myeloma - mortality ; Oncology ; Patients ; Proteasome inhibitors ; Randomization ; Rank tests ; Renal function ; Stem cell transplantation ; Stem cells ; Steroids ; Survival ; Survival Rate ; Targeted cancer therapy ; Thalidomide - analogs & derivatives ; Thalidomide - therapeutic use ; Transplants & implants ; Treatment Outcome</subject><ispartof>The Lancet (British edition), 2017-02, Vol.389 (10068), p.519-527</ispartof><rights>Elsevier Ltd</rights><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 4, 2017</rights><rights>2017. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c630t-8fe4b1226156acf0b16253e1c8bed4a9bca9d7dd965ecdd94c1ea869938781dd3</citedby><cites>FETCH-LOGICAL-c630t-8fe4b1226156acf0b16253e1c8bed4a9bca9d7dd965ecdd94c1ea869938781dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S014067361631594X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28017406$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Durie, Brian G M, Dr Prof</creatorcontrib><creatorcontrib>Hoering, Antje, PhD</creatorcontrib><creatorcontrib>Abidi, Muneer H, MD</creatorcontrib><creatorcontrib>Rajkumar, S Vincent, Prof</creatorcontrib><creatorcontrib>Epstein, Joshua, Prof</creatorcontrib><creatorcontrib>Kahanic, Stephen P, MD</creatorcontrib><creatorcontrib>Thakuri, Mohan, MD</creatorcontrib><creatorcontrib>Reu, Frederic, MD</creatorcontrib><creatorcontrib>Reynolds, Christopher M, MD</creatorcontrib><creatorcontrib>Sexton, Rachael, MS</creatorcontrib><creatorcontrib>Orlowski, Robert Z, Prof</creatorcontrib><creatorcontrib>Barlogie, Bart, Prof</creatorcontrib><creatorcontrib>Dispenzieri, Angela, Prof</creatorcontrib><title>Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. Methods In this randomised, open-label, phase 3 trial, we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group (SWOG) and National Clinical Trial Network (NCTN) institutions (both inpatient and outpatient settings). Key inclusion criteria were presence of CRAB (C=calcium elevation; R=renal impairment; A=anaemia; B=bone involvement) criteria with measurable disease (measured by assessment of free light chains), Eastern Cooperative Oncology Group (ECOG) performance status of 0–3, haemoglobin concentration 9 g/dL or higher, absolute neutrophil count 1 × 103 cells per mm3 or higher, and a platelet count of 80 000/mm3 or higher. We randomly assigned (1:1) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone (VRd group) or lenalidomide and dexamethasone alone (Rd group). Randomisation was stratified based on International Staging System stage (I, II, or III) and intent to transplant (yes vs no). The VRd regimen was given as eight 21-day cycles. Bortezomib was given at 1·3 mg/m2 intravenously on days 1, 4, 8, and 11, combined with oral lenalidomide 25 mg daily on days 1–14 plus oral dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12. The Rd regimen was given as six 28-day cycles. The standard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1–21 plus 40 mg oral dexamethasone once a day on days 1, 8, 15, and 22. The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02. Analyses were intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00644228. Findings Between April, 2008, and February, 2012, we randomly assigned 525 patients at 139 participating institutions (264 to VRd and 261 to Rd). In the randomly assigned patients, 21 patients in the VRd group and 31 in the Rd group were deemed ineligible based mainly on missing, insufficient, or early or late baseline laboratory data. Median progression-free survival was significantly improved in the VRd group (43 months vs 30 months in the Rd group; stratified hazard ratio [HR] 0·712, 96% CI 0·56–0·906; one-sided p value 0·0018). The median overall survival was also significantly improved in the VRd group (75 months vs 64 months in the Rd group, HR 0·709, 95% CI 0·524–0·959; two-sided p value 0·025). The rates of overall response (partial response or better) were 82% (176/216) in the VRd group and 72% (153/214) in the Rd group, and 16% (34/216) and 8% (18/214) of patients who were assessable for response in these respective groups had a complete response or better. Adverse events of grade 3 or higher were reported in 198 (82%) of 241 patients in the VRd group and 169 (75%) of 226 patients in the Rd group; 55 (23%) and 22 (10%) patients discontinued induction treatment because of adverse events, respectively. There were no treatment-related deaths in the Rd group, and two in the VRd group. Interpretation In patients with newly diagnosed myeloma, the addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile. Funding NIH, NCI, NCTN, Millennium Pharmaceuticals, Takeda Oncology Company, and Celgene Corporation.</description><subject>Adult</subject><subject>Aged</subject><subject>Anemia</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Autografts</subject><subject>Bortezomib</subject><subject>Bortezomib - therapeutic use</subject><subject>Calcium</subject><subject>Clinical trials</subject><subject>Dexamethasone</subject><subject>Dexamethasone - therapeutic use</subject><subject>Disease-Free Survival</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Inhibitor drugs</subject><subject>Internal Medicine</subject><subject>Lenalidomide</subject><subject>Light chains</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - mortality</subject><subject>Oncology</subject><subject>Patients</subject><subject>Proteasome inhibitors</subject><subject>Randomization</subject><subject>Rank tests</subject><subject>Renal function</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Steroids</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Targeted cancer therapy</subject><subject>Thalidomide - analogs & derivatives</subject><subject>Thalidomide - therapeutic use</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFksFuEzEQhlcIREPgEUCWuKRSF-y117vhUAQVFKRKPRREbpbXnjQu3nWwnZbw4JyZJKVAD_Riy55vfs-M_6J4yugLRpl8eUaZoKVsuJwwuc9ZPRXl7F4xYqIRZS2a2f1idIPsFY9SuqCUCknrh8Ve1VLWCCpHxc-3IWb4EXrXkSuXF8TDoL2zeGGB6MESC991D3mhUxiAXEJMq3QXpf1mdQNZ6uxgyGmnPcCVXxPr9PkQEljSr8GHXm-DYZUxISNM5iES1_eAYEatVQ4-nAd8NWXoSwPekxz1kJZeIz05-3J6TM5o0zT7r4gmGNnUhfoHJCxhKL3uwB-QJdYGhGOq0_5x8WCufYIn1_u4-Pz-3aejD-XJ6fHHozcnpZGc5rKdg-hYVUlWS23mtGOyqjkw03ZghZ52Rk9tY-1U1mBwE4aBbuV0ytumZdbycXG4012uOmzIYHtRe7WMrtdxrYJ26t_I4BbqPFyquhay5QIFJtcCMXxbQcoKW9uMQA-AI1GsrTmvK47wuHh-C70Iq4j_lFTFWdPKRlTN_yjWSlTCOTKk6h1lYkgpwvymZEbVxn9q6z-1MZfC09Z_aoZ5z_7u9ybrt-EQeL0DAKd-6SCqZNAhBj87gsnKBnfnE4e3FIx3gzPaf4U1pD_dqFQpuhPZaDC5VZjxX96hBlg</recordid><startdate>20170204</startdate><enddate>20170204</enddate><creator>Durie, Brian G M, Dr Prof</creator><creator>Hoering, Antje, PhD</creator><creator>Abidi, Muneer H, MD</creator><creator>Rajkumar, S Vincent, Prof</creator><creator>Epstein, Joshua, Prof</creator><creator>Kahanic, Stephen P, MD</creator><creator>Thakuri, Mohan, MD</creator><creator>Reu, Frederic, MD</creator><creator>Reynolds, Christopher M, MD</creator><creator>Sexton, Rachael, MS</creator><creator>Orlowski, Robert Z, Prof</creator><creator>Barlogie, Bart, Prof</creator><creator>Dispenzieri, Angela, Prof</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170204</creationdate><title>Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial</title><author>Durie, Brian G M, Dr Prof ; Hoering, Antje, PhD ; Abidi, Muneer H, MD ; Rajkumar, S Vincent, Prof ; Epstein, Joshua, Prof ; Kahanic, Stephen P, MD ; Thakuri, Mohan, MD ; Reu, Frederic, MD ; Reynolds, Christopher M, MD ; Sexton, Rachael, MS ; Orlowski, Robert Z, Prof ; Barlogie, Bart, Prof ; Dispenzieri, Angela, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c630t-8fe4b1226156acf0b16253e1c8bed4a9bca9d7dd965ecdd94c1ea869938781dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anemia</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Autografts</topic><topic>Bortezomib</topic><topic>Bortezomib - therapeutic use</topic><topic>Calcium</topic><topic>Clinical trials</topic><topic>Dexamethasone</topic><topic>Dexamethasone - therapeutic use</topic><topic>Disease-Free Survival</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Inhibitor drugs</topic><topic>Internal Medicine</topic><topic>Lenalidomide</topic><topic>Light chains</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - mortality</topic><topic>Oncology</topic><topic>Patients</topic><topic>Proteasome inhibitors</topic><topic>Randomization</topic><topic>Rank tests</topic><topic>Renal function</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Steroids</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Targeted cancer therapy</topic><topic>Thalidomide - analogs & derivatives</topic><topic>Thalidomide - therapeutic use</topic><topic>Transplants & implants</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Durie, Brian G M, Dr Prof</creatorcontrib><creatorcontrib>Hoering, Antje, PhD</creatorcontrib><creatorcontrib>Abidi, Muneer H, MD</creatorcontrib><creatorcontrib>Rajkumar, S Vincent, Prof</creatorcontrib><creatorcontrib>Epstein, Joshua, Prof</creatorcontrib><creatorcontrib>Kahanic, Stephen P, MD</creatorcontrib><creatorcontrib>Thakuri, Mohan, MD</creatorcontrib><creatorcontrib>Reu, Frederic, MD</creatorcontrib><creatorcontrib>Reynolds, Christopher M, MD</creatorcontrib><creatorcontrib>Sexton, Rachael, MS</creatorcontrib><creatorcontrib>Orlowski, Robert Z, Prof</creatorcontrib><creatorcontrib>Barlogie, Bart, Prof</creatorcontrib><creatorcontrib>Dispenzieri, Angela, Prof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>News PRO</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Global News & ABI/Inform Professional</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Newsstand Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Durie, Brian G M, Dr Prof</au><au>Hoering, Antje, PhD</au><au>Abidi, Muneer H, MD</au><au>Rajkumar, S Vincent, Prof</au><au>Epstein, Joshua, Prof</au><au>Kahanic, Stephen P, MD</au><au>Thakuri, Mohan, MD</au><au>Reu, Frederic, MD</au><au>Reynolds, Christopher M, MD</au><au>Sexton, Rachael, MS</au><au>Orlowski, Robert Z, Prof</au><au>Barlogie, Bart, Prof</au><au>Dispenzieri, Angela, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2017-02-04</date><risdate>2017</risdate><volume>389</volume><issue>10068</issue><spage>519</spage><epage>527</epage><pages>519-527</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. Methods In this randomised, open-label, phase 3 trial, we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group (SWOG) and National Clinical Trial Network (NCTN) institutions (both inpatient and outpatient settings). Key inclusion criteria were presence of CRAB (C=calcium elevation; R=renal impairment; A=anaemia; B=bone involvement) criteria with measurable disease (measured by assessment of free light chains), Eastern Cooperative Oncology Group (ECOG) performance status of 0–3, haemoglobin concentration 9 g/dL or higher, absolute neutrophil count 1 × 103 cells per mm3 or higher, and a platelet count of 80 000/mm3 or higher. We randomly assigned (1:1) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone (VRd group) or lenalidomide and dexamethasone alone (Rd group). Randomisation was stratified based on International Staging System stage (I, II, or III) and intent to transplant (yes vs no). The VRd regimen was given as eight 21-day cycles. Bortezomib was given at 1·3 mg/m2 intravenously on days 1, 4, 8, and 11, combined with oral lenalidomide 25 mg daily on days 1–14 plus oral dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12. The Rd regimen was given as six 28-day cycles. The standard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1–21 plus 40 mg oral dexamethasone once a day on days 1, 8, 15, and 22. The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02. Analyses were intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00644228. Findings Between April, 2008, and February, 2012, we randomly assigned 525 patients at 139 participating institutions (264 to VRd and 261 to Rd). In the randomly assigned patients, 21 patients in the VRd group and 31 in the Rd group were deemed ineligible based mainly on missing, insufficient, or early or late baseline laboratory data. Median progression-free survival was significantly improved in the VRd group (43 months vs 30 months in the Rd group; stratified hazard ratio [HR] 0·712, 96% CI 0·56–0·906; one-sided p value 0·0018). The median overall survival was also significantly improved in the VRd group (75 months vs 64 months in the Rd group, HR 0·709, 95% CI 0·524–0·959; two-sided p value 0·025). The rates of overall response (partial response or better) were 82% (176/216) in the VRd group and 72% (153/214) in the Rd group, and 16% (34/216) and 8% (18/214) of patients who were assessable for response in these respective groups had a complete response or better. Adverse events of grade 3 or higher were reported in 198 (82%) of 241 patients in the VRd group and 169 (75%) of 226 patients in the Rd group; 55 (23%) and 22 (10%) patients discontinued induction treatment because of adverse events, respectively. There were no treatment-related deaths in the Rd group, and two in the VRd group. Interpretation In patients with newly diagnosed myeloma, the addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile. Funding NIH, NCI, NCTN, Millennium Pharmaceuticals, Takeda Oncology Company, and Celgene Corporation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28017406</pmid><doi>10.1016/S0140-6736(16)31594-X</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2017-02, Vol.389 (10068), p.519-527 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5546834 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Aged Anemia Angiogenesis Inhibitors - therapeutic use Antineoplastic Agents - therapeutic use Autografts Bortezomib Bortezomib - therapeutic use Calcium Clinical trials Dexamethasone Dexamethasone - therapeutic use Disease-Free Survival Drug dosages Drug therapy Drug Therapy, Combination Female Hematology Hematopoietic Stem Cell Transplantation Hemoglobin Humans Immunotherapy Inhibitor drugs Internal Medicine Lenalidomide Light chains Male Medical diagnosis Middle Aged Multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - mortality Oncology Patients Proteasome inhibitors Randomization Rank tests Renal function Stem cell transplantation Stem cells Steroids Survival Survival Rate Targeted cancer therapy Thalidomide - analogs & derivatives Thalidomide - therapeutic use Transplants & implants Treatment Outcome |
| title | Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T00%3A59%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bortezomib%20with%20lenalidomide%20and%20dexamethasone%20versus%20lenalidomide%20and%20dexamethasone%20alone%20in%20patients%20with%20newly%20diagnosed%20myeloma%20without%20intent%20for%20immediate%20autologous%20stem-cell%20transplant%20(SWOG%20S0777):%20a%20randomised,%20open-label,%20phase%203%20trial&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Durie,%20Brian%20G%20M,%20Dr%20Prof&rft.date=2017-02-04&rft.volume=389&rft.issue=10068&rft.spage=519&rft.epage=527&rft.pages=519-527&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(16)31594-X&rft_dat=%3Cproquest_pubme%3E2317867427%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1865237771&rft_id=info:pmid/28017406&rft_els_id=1_s2_0_S014067361631594X&rfr_iscdi=true |