Lenalidomide Maintenance vs Observation in Newly Diagnosed Multiple Myeloma
In a UK phase III trial (Myeloma XI) reported in The Lancet Oncology, Jackson et al found that lenalidomide maintenance was associated with improved progression-free survival but not overall survival among patients with newly diagnosed multiple myeloma with at least minimal response to induction therapy. Potential overall survival benefits of lenalidomide were observed in some subgroups.
Study Details
The open-label trial, conducted at 110 National Health Service hospitals in England, Wales, and Scotland, comprises three randomization stages: induction treatment (allocation by transplantation eligibility status); intensification treatment (allocation by response to induction therapy); and maintenance treatment. The current analysis presents findings in the maintenance treatment stage.
Eligible patients for maintenance randomization had symptomatic or nonsecretory multiple myeloma, had completed assigned induction therapy, and had achieved at least a minimal response to protocol treatment, including lenalidomide. A total of 1,137 patients were randomly assigned (1:1 from January 2011 to June 2013 and 2:1 from June 2013 to August 11, 2017) to lenalidomide 10 mg on days 1 to 21 of 28-day cycles (n = 1,137) or observation (n = 834). Randomization was stratified by induction and intensification treatment and study center. The coprimary endpoints were progression-free survival and overall survival in the intention-to-treat population. Safety analyses were performed in the per-protocol population.
Progression-Free and Overall Survival
Median follow-up was 31 months. Median progression-free survival was 39 months in the lenalidomide group vs 20 months in the observation group (hazard ratio [HR] = 0.46, P < .0001). Progression-free survival was improved with lenalidomide among all prespecified subgroups.
Overall survival at 3 years among all patients was 78.6% vs 75.8% (HR = 0.87, P = .15).
In prespecified subgroup analyses, 3-year overall survival was improved with lenalidomide among the 62% to 64% of patients eligible for autologous stem cell transplantation (87.5% vs 80.2%, HR = 0.69, P = .014) but not in transplantation-ineligible patients (66.8% vs 69.8%, HR = 1.02, P = .88). Cytogenetic risk assessment was available for 39% of patients in each group; 3-year overall survival was 86.4% vs 81.3% among standard-risk patients, 74.9% vs 63.7% among high-risk patients, and 62.9% vs 43.5% among ultra–high-risk patients; however, as noted by the investigators, “Since these subgroup analyses results were not powered they should be interpreted with caution.”
The most common grade 3 or 4 adverse events in the lenalidomide group were hematologic events, including neutropenia (33%), thrombocytopenia (7%), and anemia (4%). Serious adverse events occurred in 45% of the lenalidomide group vs 17% of the observation group, with the most common in both groups being infection. The 3-year cumulative incidence of second primary malignancies was 5.3% in the lenalidomide group vs 3.1% in the observation group. No deaths in the lenalidomide group were deemed as treatment-related.
The investigators concluded, “Maintenance therapy with lenalidomide significantly improved progression-free survival in patients with newly diagnosed multiple myeloma compared with observation, but did not improve overall survival in the intention-to-treat analysis of the whole trial population. The manageable safety profile of this drug and the encouraging results in subgroup analyses of patients across all cytogenetic risk groups support further investigation of maintenance lenalidomide in this setting.”
Graham H. Jackson, MD, of the Northern Institute for Cancer Research, Newcastle University, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK, Celgene, Amgen, Merck, and Myeloma UK. The study authors’ full disclosures can be found at thelancet.com.
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