EC Approves Maintenance Lenalidomide for Myeloma

The European Commission has expanded the indication for lenalidomide (Revlimid) to include use as a maintenance therapy for patients with multiple myeloma following autologous hematopoietic stem cell transplant (auto-HSCT), according to Celgene, the manufacturer of the treatment.

The approval, which follows a positive opinion from the Committee for Medicinal Products for Human Use, is based on data from from 2 large trials (1000+ patients each) that compared maintenance lenalidomide versus no maintenance after auto-HSCT. The primary endpoint of both studies was progression-free survival (PFS).

In CALGB 100104, after 81.6 months of follow up, the median PFS was 56.9 months (95% CI, 41.9-71.7) in the lenalidomide arm versus 29.4 months (95% CI, 20.7-35.5) in the placebo arm (HR, 0.61; 95% CI, 0.48-0.76; P <.001). In the IFM 2005-02 trial, after 96.7 months of follow up, the median PFS was 44.4 months (95% CI, 39.6-52.0) with lenalidomide maintenance versus 23.8 months (95% CI, 21.2-27.3) with placebo (HR, 0.57; 95% CI, 0.47-0.68; P <.001).

The median overall survival (OS) in CALGB 100104 was 111.0 months (95% CI, 101.8 to not estimable) in the lenalidomide group versus 84.2 months (95% CI, 71.0-102.7) in the placebo arm (HR, 0.61; 95% CI, 0.46-0.81; P <.001). In the IFM 2005-02 study, the median OS was 105.9 months (95% CI, 88.8 to not estimable) versus 88.1 months (95% CI, 80.7-108.4), respectively (HR, 0.90; 95% CI, 0.72-1.13; P = 0.355).

"We are glad to provide a treatment option for these patients with multiple myeloma, who have previously had no licensed medicine available to them for maintenance treatment following ASCT. This latest approval underlines the important role of Revlimid in the treatment of multiple myeloma, extending its use across the disease spectrum, and demonstrating our commitment to multiple myeloma patients. We continue to invest in research and development as we strive to turn multiple myeloma—and other currently incurable diseases—into manageable conditions,” Tuomo Pätsi, president of Celgene European and International Operations, said in a statement.

The doubled-blind phase III CALGB 100104 trial randomized 460 patients with multiple myeloma to maintenance lenalidomide or placebo after first-line chemotherapy and ASCT. Lenalidomide was started at 10 mg daily and elevated to 15 mg daily at 3 months for patients who tolerated the initial treatment. The trial was conducted at 47 locations in the United States. The primary endpoint was time to tumor progression.

IFM 2005-02 was a phase III double-blind trial in which 614 treatment-naïve patients with multiple myeloma who had received induction chemotherapy and ASCT were randomized in a 1:1 ratio to consolidation lenalidomide (25 mg/day on days 1-21 of each 28-day cycle, for 2 cycles) followed by placebo or maintenance lenalidomide (10 mg/day induction dose increased to 15 mg/day at 3 months if tolerated). The study was conducted at 78 centers in France, Belgium, and Switzerland, and had a primary endpoint of posttransplant progression-free survival.

The most common all-grade adverse events (AEs) across the the 2 trials (CALGB 100104, IFM 2005-02, respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%). The most common grade 3/4 AEs across both trials included neutropenia, thrombocytopenia, and leukopenia.

A meta-analysis of data pooled from CALGB 100104, IFM 2005-02, and a third randomized phase III trial, GIMEMA-RVMM-PI-209, was presented at the 2016 ASCO Annual Meeting. The findings showed that maintenance lenalidomide following frontline treatment with high-dose melphalan and ASCT reduced the risk of death by 26% versus placebo or no maintenance in patients with multiple myeloma. The 7-year OS rate was 62% with maintenance lenalidomide versus 50% in patients who did not receive the therapy.

Maintenance lenalidomide is also approved by the FDA for use in this setting.