Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis

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 Myélome 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.

Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM

“…8 No new safety signals were observed, although collection of registry safety data is not as comprehensive as in clinical studies.…”

“…Notably, clinical consensus assesses the risk of SPM as being outweighed by the risk of disease progression without lenalidomide maintenance treatment. 3,8,15,16 Other potential limitations of registries should be acknowledged, including the nonrandomized nature of the study, the lack of mandate for specific treatments (investigator selection) or response assessments, limitations in collection of AE data (lack of information on low grade events), and variations in treatment duration and intensity. As in any observational study, there is also potential for missing and erroneous data.…”

“…7 A recent meta-analysis in patients with NDMM confirmed the PFS benefit and the significant OS benefit of post-ASCT lenalidomide maintenance therapy when compared with placebo or observation (not reached [NR] vs 86.0 months, respectively; HR, 0.75 [95% CI, 0.63-0.90]; P 5 .001). 8 However, the impact of lenalidomide maintenance on survival outcomes has not been assessed thoroughly in the community setting, in which greater representation of unselected patients (typically including those who are older and sicker) would be expected compared with clinical trials.…”

NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018

“…Vanderbilt-Ingram Cancer Center; 18 Stanford Cancer Institute; 19 UCSF Helen Diller Family Comprehensive Cancer Center; 20 Roswell Park Cancer Institute; 21 Patient Advocate; 22 …”

Ixazomib in the treatment of relapsed multiple myeloma

“…По данным ОНКОГЕМАТОЛОГИЯ метаанализа 3 больших проспективных исследований (n = 1208), длительная поддерживающая терапия леналидо-мидом у пациентов с впервые диагностированной ММ, получивших в первой линии ауто-ТГСК, имеет несомненное преимущество по сравнению с фиксированной по време-ни, когда поддерживающая терапия не проводится [4]. На поддерживающей терапии леналидомидом медиана выживаемости без прогрессирования (ВБП) составила 52,8 мес.…”