Meta-Analysis Upholds Benefit in Progression-Free Survival, but Not Overall Survival, With Lenalidomide Maintenance

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Preet Paul Singh, MD

The subset of patients benefitting the most from lenalidomide maintenance is not yet defined, and the risks and benefits should be discussed with all patients.

—Preet Paul Singh, MD

Multiple myeloma patients derived a benefit from maintenance lenalidomide (Revlimid) treatment in terms of progression-free but not overall survival, according to a meta-analysis of four key trials presented at the 2013 American Society of Hematology (ASH) Annual Meeting.1 The study does little to settle the debate over the value of maintenance in prolonging survival.

“The subset of patients benefitting the most from lenalidomide maintenance is not yet defined, and the risks and benefits should be discussed with all patients,” said Preet Paul Singh, MD, from Mayo Clinic, Rochester, Minnesota, who presented the findings.

Four Randomized Trials

The Mayo Clinic investigators performed the systematic review and meta-analysis of existing outcome data—including updated findings presented at this meeting—to evaluate the role of lenalidomide given continuously following induction or transplant until relapse. They included four randomized controlled trials involving 1,935 patients: the Intergroupe Francophone du Myelome (IFM) 2005-02 trial, the Cancer and Leukemia Group B (CALGB) 100104 trial, Celgene’s MM-015 trial, and the Fondazione Neoplasie Sangue Onlus–sponsored RV-MM-PI209. Patients received lenalidomide at 10 mg daily (increased to 15 mg daily in some trials, if tolerated) after induction or transplant, continued until progression.

The Mayo Clinic researchers found no heterogeneity for estimates of progression-free survival but considerable heterogeneity for the overall survival estimate among the trials.

“All four studies showed an improvement in progression-free survival, with an overall 51% reduction in risk of progression (P < .001),” Dr. Singh reported. “There was a small [nonsignificant] improvement in overall survival with lenalidomide maintenance, with two studies showing a benefit and two not showing one, resulting in a modest 23% reduction in risk (P = .071).”

In the individual studies, a survival benefit was demonstrated in CALGB 100104 (hazard ratio [HR] = 0.61, P = .008) and RV-MM-PI209 (HR = 0.620, P = .018), but not in MM-015 (HR = 0.79, P = .251) and IMF 2005-02 (HR = 1.06, P = .664).

Additional Data

In patients who actually received a transplant (analyses from IFM 2005-02 and CALGB 100104), a nonsignificant 18% reduction in risk was observed (P = .462).  It should be noted that this estimate did not include survival data from the transplant arm of the RV-MM-P1209 study, and will be updated when complete results of this study are published. The odds of achieving a very good partial response or better were 28% higher in the maintenance arm, but again this lacked statistical significance (P = .329).

Secondary primary malignancies were significantly increased with lenalidomide maintenance, he said. The increase was 62% (P = .006), and there was no heterogeneity among the studies. Other complications were also increased, including a 4.9-fold increased risk of neutropenia (P < .001), a 2.7-fold increase in thrombocytopenia (P < .001), a 2.3-fold risk in fatigue (P = .01) and a 3.2-fold increase in venous thromboembolism (P = .02).

Before making a recommendation for using or not using lenalidomide, Dr. Singh suggested “waiting for longer follow-up and subgroup analyses, once complete data are available from all the trials.” ■

Disclosure: Dr. Singh reported no potential conflicts of interest.


1. Singh PP, Kumar S, LaPlant B, et al: Lenalidomide maintenance therapy in multiple myeloma: A meta-analysis of randomized trials. 2013 American Society of Hematology Annual Meeting. Abstract 407. Presented December 9, 2013.