Lenalidomide vs Observation in Asymptomatic Smoldering Multiple Myeloma

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In a phase III trial reported in the Journal of Clinical Oncology, Sagar Lonial, MD, and colleagues found that lenalidomide significantly improved progression-free survival vs observation in patients with intermediate- or high-risk smoldering multiple myeloma. As noted by the investigators, observation is the current standard of care in this setting.

Sagar Lonial, MD

Sagar Lonial, MD

Study Details

In the open-label multicenter trial, 182 patients with asymptomatic disease were randomly assigned between February 2013 and July 2017 to receive lenalidomide at 25 mg on days 1 to 21 of every 28-day cycle (n = 90) or to observation (n = 92), with treatment or observation continuing until disease progression, unacceptable toxicity, or patient withdrawal. A determination of progression to symptomatic disease required biochemical progression as defined by International Myeloma Working Group (IMWG) criteria and evidence of end-organ damage considered to be related to myeloma as indicated by one or more of the following: hypercalcemia, renal insufficiency, anemia, or bone disease.

Response was assessed according to IMWG criteria. The primary endpoint was progression-free survival.

Progression-Free Survival

Median follow-up was 35 months. Median treatment duration in the lenalidomide group was 23 cycles. Objective response was observed in 50% of the lenalidomide group vs 0% of the observation group. Progression-free survival was significantly prolonged in the lenalidomide group (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.12–0.62, P = .002), with 1-, 2-, and 3-year rates of 98% vs 89%, 93% vs 76%, and 91% vs 66%. At the time of analysis, six patients had died—two in the lenalidomide group vs four in the observation group (HR = 0.46, 95% CI = 0.08–2.53).


  • Lenalidomide significantly prolonged progression-free survival vs observation.
  • Progression-free survival was 91% vs 66% at 3 years.

Adverse Events

Grade 3 or 4 hematologic or nonhematologic adverse events occurred in 36 patients (41%) in the lenalidomide group, with nonhematologic events occurring in 25 (28%); the most common were decreased neutrophils (14%), infection (10%), hypertension (9%), and fatigue (7%). Grade 3 or 4 adverse events occurred in four patients (5%) in the observation group. Adverse events led to lenalidomide discontinuation in 18 patients (20%). The 3-year cumulative incidence of second primary cancers was 5.2% in the lenalidomide group and 3.5% in the observation group.

The investigators concluded, “Early intervention with lenalidomide in smoldering multiple myeloma significantly delays progression to symptomatic multiple myeloma and the development of end-organ damage.”

Dr. Lonial, of Winship Cancer Institute of Emory University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants. For full disclosures of the study authors, visit


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.