Revlimid After Stem Cell Transplant Improves Survival in Myeloma

Patients with multiple myeloma saw a 26 percent decrease in risk of death when they took maintenance Revilmid (lenalidomide) after frontline treatment with high-dose Alkeran (melphalan) and autologous stem cell transplant (ASCT), when compared with placebo or no maintenance, according to a meta-analysis presented at American Society of Clinical Oncology’s (ASCO) 2016 Annual Meeting.

The analysis included pooled data from 1,209 patients with newly diagnosed multiple myeloma enrolled across three phase 3 randomized trials: CALGB (Alliance) 100104, IFM 2005-02 and GIMEMA-RVMM-PI-209. The seven-year overall survival (OS) rate was 62 percent with maintenance Revlimid versus 50 percent in patients who did not receive the therapy.

“Lenalidomide maintenance following autologous stem cell transplant can now be considered a standard of care for people with multiple myeloma,” Philip McCarthy, senior author on the meta-analysis and principal investigator of the CALGB study said in a statement released during the ASCO meeting.

“The improvements over the last decade in terms of both survival and quality of life for patients with this disease are striking, and very encouraging,” added McCarthy, who is director of Blood & Marrow Transplant at Roswell Park Cancer Institute.

In the pooled analysis, 605 patients had been randomized between 2005 and 2009 to Revlimid maintenance and 604 patients received placebo or no maintenance. Baseline characteristics were well balanced between the two arms. Eighty-two percent of patients received single ASCT and 18 percent received tandem ASCT. Following induction therapy and ASCT, a complete response (CR) or very good partial response (VGPR) was reached by 55 percent of the patients.

At a median follow-up of 80 months, the median OS had not been reached in the maintenance Revlimid arm versus 86 months in the control arm. The researchers estimated this represents a 2.5-year OS benefit with maintenance Revlimid. The reduction in the risk of death with Revlimid was 14 percent in patients who had a partial response or less to induction treatment and ASCT, and 30 percent in patients who achieved a CR or VGPR.

The five-year OS rate was 71 percent with maintenance Revlimid versus 66 percent in the control arm. The six-year OS rates were 65 percent versus 58 percent, respectively.

The OS benefit observed in the pooled analysis is consistent with previously reported progression-free survival data, which showed that in each of the phase 3 studies, maintenance Revlimid reduced the risk of disease progression or death by approximately 50 percent.

"Lenalidomide has consistently demonstrated improvement in progression-free survival in this setting," lead author of the IFM study, Michel Attal, University of Toulouse, said in a statement released during the ASCO conference. "The improved overall survival shown by this meta-analysis further supports the positive benefit-risk ratio observed in the individual phase 3 studies."

The risk of developing a hematologic or solid tumor second primary malignancy (SPM) was higher in patients receiving Revlimid, with hazard ratios of 2.03 and 1.71, respectively. There were 36 hematologic SPMs in the Revlimid cohort compared with 17 in the control group. Cases of solid tumor SPMs were 43 and 25, respectively.

McCarthy noted, however, that, “The overall survival benefit of lenalidomide maintenance outweighs the risk of developing an SPM.”

The doubled-blind phase 3 CALGB (Alliance) 100104 trial randomized patients with multiple myeloma to maintenance Revlimid or placebo after first-line chemotherapy and ASCT. Revlimid was started at 10 mg daily and elevated to 15 mg daily at three 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 3 double-blind trial in which treatment-naïve patients with multiple myeloma who had received induction chemotherapy and ASCT were randomized in a 1-1 ratio to consolidation Revlimid (25 mg/day on days one to 21 of each 28-day cycle, for two cycles) followed by placebo or maintenance Revlimid (10 mg/day induction dose increased to 15 mg/day at three months if tolerated). The study was conducted at 78 centers in France, Belgium and Switzerland, and had a primary endpoint of posttrantplant PFS.

In the the double-blind, open-label phase 3 GIMEMA-RVMM-PI-209 trial, newly diagnosed patients with multiple myeloma who received standard induction with Revlimid plus dexamethasone were then treated with ASCT or MPR (Alkeran, prednisone and Revlimid), followed by maintenance Revlimid or no treatment. The trial was conducted at 62 locations in Italy and Israel. The primary objective was PFS and the secondary outcome measure was the efficacy and safety of maintenance Revlimid.

Commenting on the pooled analysis results, the lead investigator of the GIMEMA study, Antonio Palumbo, of the University of Torino, said, “The results of this meta-analysis reinforce the long-term benefit that lenalidomide maintenance therapy has demonstrated in myeloma patients who receive an autologous stem cell transplant within the large, phase 3 studies individually.”