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

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).

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 jco.ascopubs.org.