Maintenance Treatment and Survival in Patients with Myeloma

A Systematic Review and Network Meta-analysis

Francesca Gay, Graham Jackson, Laura Rosiñol, Sarah A. Holstein, Philippe Moreau, Stefano Spada, Faith Davies, Juan José Lahuerta, Xavier Leleu, Sara Bringhen, Andrea Evangelista, Cyrille Hulin, Ugo Panzani, David A. Cairns, Francesco Di Raimondo, Margaret Macro, Anna Marina Liberati, Charlotte Pawlyn, Massimo Offidani, Andrew Spencer & 11 others Roman Hájek, Evangelos Terpos, Gareth J. Morgan, Joan Bladé, Pieter Sonneveld, Jesús San-Miguel, Philip L. McCarthy, Heinz Ludwig, Mario Boccadoro, Maria Victoria Mateos, Michel Attal

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Importance: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. Objective: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. Data Sources: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. Study Selection: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. Data Extraction and Synthesis: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). Main Outcomes and Measures: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). Results: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.

Original languageEnglish
Pages (from-to)1389-1397
Number of pages9
JournalJAMA Oncology
Volume4
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Cite this

Gay, F., Jackson, G., Rosiñol, L., Holstein, S. A., Moreau, P., Spada, S., ... Attal, M. (2018). Maintenance Treatment and Survival in Patients with Myeloma: A Systematic Review and Network Meta-analysis. JAMA Oncology, 4(10), 1389-1397. https://doi.org/10.1001/jamaoncol.2018.2961
Gay, Francesca ; Jackson, Graham ; Rosiñol, Laura ; Holstein, Sarah A. ; Moreau, Philippe ; Spada, Stefano ; Davies, Faith ; Lahuerta, Juan José ; Leleu, Xavier ; Bringhen, Sara ; Evangelista, Andrea ; Hulin, Cyrille ; Panzani, Ugo ; Cairns, David A. ; Di Raimondo, Francesco ; Macro, Margaret ; Liberati, Anna Marina ; Pawlyn, Charlotte ; Offidani, Massimo ; Spencer, Andrew ; Hájek, Roman ; Terpos, Evangelos ; Morgan, Gareth J. ; Bladé, Joan ; Sonneveld, Pieter ; San-Miguel, Jesús ; McCarthy, Philip L. ; Ludwig, Heinz ; Boccadoro, Mario ; Mateos, Maria Victoria ; Attal, Michel. / Maintenance Treatment and Survival in Patients with Myeloma : A Systematic Review and Network Meta-analysis. In: JAMA Oncology. 2018 ; Vol. 4, No. 10. pp. 1389-1397.
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title = "Maintenance Treatment and Survival in Patients with Myeloma: A Systematic Review and Network Meta-analysis",
abstract = "Importance: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. Objective: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. Data Sources: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. Study Selection: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. Data Extraction and Synthesis: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95{\%} credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). Main Outcomes and Measures: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). Results: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95{\%} CrI, 0.28-0.53] and 0.47 [95{\%} CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74{\%}). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95{\%} CrI, 0.51-1.16; MedR, 2; PbBT, 38{\%}), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.",
author = "Francesca Gay and Graham Jackson and Laura Rosi{\~n}ol and Holstein, {Sarah A.} and Philippe Moreau and Stefano Spada and Faith Davies and Lahuerta, {Juan Jos{\'e}} and Xavier Leleu and Sara Bringhen and Andrea Evangelista and Cyrille Hulin and Ugo Panzani and Cairns, {David A.} and {Di Raimondo}, Francesco and Margaret Macro and Liberati, {Anna Marina} and Charlotte Pawlyn and Massimo Offidani and Andrew Spencer and Roman H{\'a}jek and Evangelos Terpos and Morgan, {Gareth J.} and Joan Blad{\'e} and Pieter Sonneveld and Jes{\'u}s San-Miguel and McCarthy, {Philip L.} and Heinz Ludwig and Mario Boccadoro and Mateos, {Maria Victoria} and Michel Attal",
year = "2018",
month = "10",
day = "1",
doi = "10.1001/jamaoncol.2018.2961",
language = "English",
volume = "4",
pages = "1389--1397",
journal = "JAMA Oncology",
issn = "2374-2437",
publisher = "American Medical Association (AMA)",
number = "10",

}

Gay, F, Jackson, G, Rosiñol, L, Holstein, SA, Moreau, P, Spada, S, Davies, F, Lahuerta, JJ, Leleu, X, Bringhen, S, Evangelista, A, Hulin, C, Panzani, U, Cairns, DA, Di Raimondo, F, Macro, M, Liberati, AM, Pawlyn, C, Offidani, M, Spencer, A, Hájek, R, Terpos, E, Morgan, GJ, Bladé, J, Sonneveld, P, San-Miguel, J, McCarthy, PL, Ludwig, H, Boccadoro, M, Mateos, MV & Attal, M 2018, 'Maintenance Treatment and Survival in Patients with Myeloma: A Systematic Review and Network Meta-analysis', JAMA Oncology, vol. 4, no. 10, pp. 1389-1397. https://doi.org/10.1001/jamaoncol.2018.2961

Maintenance Treatment and Survival in Patients with Myeloma : A Systematic Review and Network Meta-analysis. / Gay, Francesca; Jackson, Graham; Rosiñol, Laura; Holstein, Sarah A.; Moreau, Philippe; Spada, Stefano; Davies, Faith; Lahuerta, Juan José; Leleu, Xavier; Bringhen, Sara; Evangelista, Andrea; Hulin, Cyrille; Panzani, Ugo; Cairns, David A.; Di Raimondo, Francesco; Macro, Margaret; Liberati, Anna Marina; Pawlyn, Charlotte; Offidani, Massimo; Spencer, Andrew; Hájek, Roman; Terpos, Evangelos; Morgan, Gareth J.; Bladé, Joan; Sonneveld, Pieter; San-Miguel, Jesús; McCarthy, Philip L.; Ludwig, Heinz; Boccadoro, Mario; Mateos, Maria Victoria; Attal, Michel.

In: JAMA Oncology, Vol. 4, No. 10, 01.10.2018, p. 1389-1397.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Maintenance Treatment and Survival in Patients with Myeloma

T2 - A Systematic Review and Network Meta-analysis

AU - Gay, Francesca

AU - Jackson, Graham

AU - Rosiñol, Laura

AU - Holstein, Sarah A.

AU - Moreau, Philippe

AU - Spada, Stefano

AU - Davies, Faith

AU - Lahuerta, Juan José

AU - Leleu, Xavier

AU - Bringhen, Sara

AU - Evangelista, Andrea

AU - Hulin, Cyrille

AU - Panzani, Ugo

AU - Cairns, David A.

AU - Di Raimondo, Francesco

AU - Macro, Margaret

AU - Liberati, Anna Marina

AU - Pawlyn, Charlotte

AU - Offidani, Massimo

AU - Spencer, Andrew

AU - Hájek, Roman

AU - Terpos, Evangelos

AU - Morgan, Gareth J.

AU - Bladé, Joan

AU - Sonneveld, Pieter

AU - San-Miguel, Jesús

AU - McCarthy, Philip L.

AU - Ludwig, Heinz

AU - Boccadoro, Mario

AU - Mateos, Maria Victoria

AU - Attal, Michel

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Importance: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. Objective: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. Data Sources: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. Study Selection: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. Data Extraction and Synthesis: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). Main Outcomes and Measures: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). Results: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.

AB - Importance: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. Objective: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. Data Sources: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. Study Selection: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. Data Extraction and Synthesis: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). Main Outcomes and Measures: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). Results: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.

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U2 - 10.1001/jamaoncol.2018.2961

DO - 10.1001/jamaoncol.2018.2961

M3 - Review Article

VL - 4

SP - 1389

EP - 1397

JO - JAMA Oncology

JF - JAMA Oncology

SN - 2374-2437

IS - 10

ER -