(ChemotherapyAdvisor) – Maintenance therapy that included lenalidomide extended progression-free survival (PFS) in patients with multiple myeloma, three studies reported in the May 10, 2012, issue of the New England Journal of Medicine have concluded.

The multicenter, randomized, double-blind, placebo-controlled Phase 3 trials examined continuous lenalidomide treatment for patients with newly diagnosed multiple myeloma and lenalidomide as maintenance therapy after stem-cell transplantation.

  • Study 1 compared melphalan–prednisone–lenalidomide induction followed by lenalidomide maintenance (MPR-R; n=152) with melphalan–prednisone–lenalidomide (MPR; n=153) or melphalan–prednisone (MP; n=154) followed by placebo in patients ≥65 years of age with newly diagnosed multiple myeloma ineligible for transplantation. Median follow-up was 30 months. Median PFS was significantly longer with MPR-R (31 months) than with MPR (14 months; HR, 0.49; P<0.001) or MP (13 months; HR, 0.40; P<0.001). The greatest benefit was observed in patients ages 65 to 75 years.
  • Study 2 randomly assigned 460 patients <71 years of age with complete, partial, or marginal response or stable disease 100 days post-stem-cell transplantation to lenalidomide 10mg/day (starting dose; range, 5 to 15mg/day) or placebo, administered until disease progression. Median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%).
  • Study 3 randomly assigned 614 patients <65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with lenalidomide (10mg/day for the first 3 months, increased to 15mg/day if tolerated) or placebo until relapse. Lenalidomide maintenance therapy was found to improve median PFS (41 months vs. 23 months with placebo; HR, 0.50; P<0.001). “This benefit was observed across all patient subgroups, including those based on the β2-microglobulin level, cytogenetic profile, and response after transplantation,” the investigators noted. Incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group vs. 1.2 per 100 patient-years in the placebo group (P=0.002).

An accompanying editorial found these studies to provide “compelling evidence of improvement” in PFS but “raise several critical questions,” including whether PFS is an appropriate primary endpoint in maintenance trials; whether lenalidomide maintenance therapy is safe, given the increased incidence of primary cancers; and whether it is cost-effective. The cost of lenalidomide is $163,381 annually “for the average patient.”

Study 1 (ClinicalTrials.gov number: NCT00405756)

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Study 2 (ClinicalTrials.gov number: NCT00114101)

Study 3 (ClinicalTrials.gov number: NCT00430365)