Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis

Philip L. McCarthy, Sarah A Holstein, Maria Teresa Petrucci, Paul G. Richardson, Cyrille Hulin, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C. Anderson, Denis Caillot, Francesca Gay, Philippe Moreau, Gerald Marit, Sin Ho Jung, Zhinuan Yu, Benjamin Winograd, Robert D. Knight, Antonio Palumbo, Michel Attal

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Abstract

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Mye Lome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.

Original languageEnglish (US)
Pages (from-to)3279-3289
Number of pages11
JournalJournal of Clinical Oncology
Volume35
Issue number29
DOIs
StatePublished - Oct 10 2017

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Stem Cell Transplantation
Multiple Myeloma
Meta-Analysis
Maintenance
Placebos
Observation
Disease-Free Survival
Randomized Controlled Trials
Survival
lenalidomide
Second Primary Neoplasms
Incidence
Documentation
Disease Progression
Leukemia
Databases
Mortality

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma : A meta-analysis. / McCarthy, Philip L.; Holstein, Sarah A; Petrucci, Maria Teresa; Richardson, Paul G.; Hulin, Cyrille; Tosi, Patrizia; Bringhen, Sara; Musto, Pellegrino; Anderson, Kenneth C.; Caillot, Denis; Gay, Francesca; Moreau, Philippe; Marit, Gerald; Jung, Sin Ho; Yu, Zhinuan; Winograd, Benjamin; Knight, Robert D.; Palumbo, Antonio; Attal, Michel.

In: Journal of Clinical Oncology, Vol. 35, No. 29, 10.10.2017, p. 3279-3289.

Research output: Contribution to journalArticle

McCarthy, PL, Holstein, SA, Petrucci, MT, Richardson, PG, Hulin, C, Tosi, P, Bringhen, S, Musto, P, Anderson, KC, Caillot, D, Gay, F, Moreau, P, Marit, G, Jung, SH, Yu, Z, Winograd, B, Knight, RD, Palumbo, A & Attal, M 2017, 'Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis', Journal of Clinical Oncology, vol. 35, no. 29, pp. 3279-3289. https://doi.org/10.1200/JCO.2017.72.6679
McCarthy, Philip L. ; Holstein, Sarah A ; Petrucci, Maria Teresa ; Richardson, Paul G. ; Hulin, Cyrille ; Tosi, Patrizia ; Bringhen, Sara ; Musto, Pellegrino ; Anderson, Kenneth C. ; Caillot, Denis ; Gay, Francesca ; Moreau, Philippe ; Marit, Gerald ; Jung, Sin Ho ; Yu, Zhinuan ; Winograd, Benjamin ; Knight, Robert D. ; Palumbo, Antonio ; Attal, Michel. / Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma : A meta-analysis. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 29. pp. 3279-3289.
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abstract = "Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Mye Lome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95{\%} CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95{\%} CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.",
author = "McCarthy, {Philip L.} and Holstein, {Sarah A} and Petrucci, {Maria Teresa} and Richardson, {Paul G.} and Cyrille Hulin and Patrizia Tosi and Sara Bringhen and Pellegrino Musto and Anderson, {Kenneth C.} and Denis Caillot and Francesca Gay and Philippe Moreau and Gerald Marit and Jung, {Sin Ho} and Zhinuan Yu and Benjamin Winograd and Knight, {Robert D.} and Antonio Palumbo and Michel Attal",
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TY - JOUR

T1 - Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma

T2 - A meta-analysis

AU - McCarthy, Philip L.

AU - Holstein, Sarah A

AU - Petrucci, Maria Teresa

AU - Richardson, Paul G.

AU - Hulin, Cyrille

AU - Tosi, Patrizia

AU - Bringhen, Sara

AU - Musto, Pellegrino

AU - Anderson, Kenneth C.

AU - Caillot, Denis

AU - Gay, Francesca

AU - Moreau, Philippe

AU - Marit, Gerald

AU - Jung, Sin Ho

AU - Yu, Zhinuan

AU - Winograd, Benjamin

AU - Knight, Robert D.

AU - Palumbo, Antonio

AU - Attal, Michel

PY - 2017/10/10

Y1 - 2017/10/10

N2 - Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Mye Lome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.

AB - Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Mye Lome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.

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