Patients with newly diagnosed multiple myeloma who received lenalidomide as maintenance therapy following an autologous stem cell transplant (ASCT) had significantly better progression-free and overall survival, compared with patients who received placebo or observation after transplant, results of a meta-analysis showed.
Among 1,208 patients in an intention-to-treat analysis, the median progression-free survival (PFS) for patients who received lenalidomide maintenance was nearly double that of patients treated with placebo or observation alone after ASCT, and the median overall survival for patients on maintenance had not been reached after a median follow-up of 79.5 months, reported Phillip J McCarthy, MD , of Roswell Park Cancer Institute in Buffalo, N.Y., and his colleagues.
“This study demonstrates a statistically significant and clinically meaningful improvement in OS with lenalidomide maintenance. With new, highly active, triplet induction regimens enhancing depth and duration of response, as well as ongoing studies evaluating the optimal timing of ASCT, the use of lenalidomide maintenance for transplantation-eligible patients can be considered a standard of care,” they wrote in the Journal of Clinical Oncology.
The authors drew on data from three randomized controlled trials in which patients with newly diagnosed multiple myeloma underwent ASCT followed by lenalidomide maintenance, placebo, or observation. The trials were the Cancer and Leukemia Group B ( CALGB) 100104 , Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) RV-MM-PI-209 , and Intergroupe Francophone du Myelome (IFM) 2005-02 .
Because all three studies had PFS as the primary endpoint and were not powered to detect an overall survival (OS) benefit, the investigators conducted a meta-analysis to get a better sense of the effect of maintenance on both PFS and OS.
The meta-analysis included 605 patients randomized to lenalidomide maintenance and 603 to placebo or observation.
The median PFS was 52.8 months with lenalidomide, vs. 23.5 months for placebo or observation (hazard ratio [HR] 0.48; 95% confidence interval, 0.41-0.55).
After a median follow-up of 79.5 months for all survivors, the median OS for patients on lenalidomide was not reached, compared with 86.0 months for placebo/observation (HR, 0.75, P = .001).
An analysis of safety data from the CALGB and IFM studies (GIMEMA data were not available) showed that second primary malignancies occurring before disease progression were more frequent in the lenalidomide maintenance group, at 5.3%, compared with 0.8%. In contrast, the cumulative incidence rates of progression, death, or myeloma-specific death were all higher with placebo or observation versus lenalidomide maintenance, the investigators found.
Although lenalidomide maintenance adds to the cost of care, the “costs of maintenance therapy should be weighed against the costs of shorter survival, earlier progression, and earlier use of subsequent lines of therapies for patients without maintenance,” the researchers wrote.
The study was supported by Celgene. Dr. McCarthy and multiple coauthors reported consulting/advisory roles, honoraria, travel support, and/or research support from the company.