CHICAGO — Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant (ASCT) significantly prolonged overall survival in patients with multiple myeloma compared with no maintenance, a meta-analysis of 3 randomized controlled trials presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting has found.1
“Lenalidomide maintenance is feasible for long-term disease control after ASCT,” said Philip L. McCarthy, MD, Roswell Park Cancer Institute, Buffalo, New York, and “can be considered a standard of care.”
This benefit was demonstrated in patients in all response categories, including in those who achieved complete response. Although several studies have shown that use of lenalidomide post-ASCT reduces risk of disease progression or death by approximately 50%, none were powered to report overall survival.
The study’s objective was “to assess the effect of post-ASCT lenalidomide maintenance on overall survival using a pooled analysis of primary-source patient data,” he said.
The prospective meta-analysis identified 17 trials that used lenalidomide post-ASCT for patients with newly diagnosed multiple myeloma, 3 of which — IFM 2005-02, CALGB 100104 (Alliance), and GIMEMA RV-MM-PI-209 — met prespecified inclusion criteria. This included patient-level data, a control arm, and that “database lock had previously occurred for primary efficacy analysis.” A March 2015 cutoff “allowed for targeting a 20-month improvement in median overall survival” at a treatment effect with a hazard ratio (HR) of 0.78, Dr. McCarthy reported.
In the 3 trials, 1209 patients were randomly assigned from 2005 to 2009 to receive lenalidomide 10 mg/day on days 1 to 21 of 28 (GIMEMA) or days 1 to 28 of 28 (IFM and CALGB) (n = 605) or placebo (n = 604), defined as the control arm. In the pooled data, baseline characteristics were generally balanced. At a median follow-up of 6.6 years, 491 patients (41%) had died.
Following induction and single (82%) or tandem (18%) ASCT, 55% of patients had achieved a complete response or a very good partial response. Among those who had received lenalidomide, median overall survival was not reached vs 86.0 months for the control group (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.89; log-rank P = .001). Compared with the control group, overall survival was longer in the lenalidomide group at 5 years (71% vs 66%), 6 years (65% vs 58%), and 7 years (62% vs 50%).
“Lenalidomide maintenance significantly prolongs overall survival post-ASCT,” Dr. McCarthy said. The hazard ratio was 0.74 (95% CI, 0.62-0.89; log-rank P = .001), with an “estimated 2.5-year improvement in median overall survival.” This overall survival benefit “outweighs the risk of developing a secondary primary malignancy,” he added.
“Overall survival benefit was generally consistent across subgroups,” the results showed. The Pignon test showed quantitative heterogeneity across trials (P = .047), with a difference in the magnitude of the treatment effects, primarily between the CALGB and IFM trials. Potential reasons for this heterogeneity include imbalances in prestudy characteristics between treatment arms within the individual studies, different induction regimens and pretransplant consolidations, differences in study conduct after unblinding; or differences in frequency and type of second-line therapy,” Dr. McCarthy concluded.
1. Attal M, Palumbo A, Holstein SA, et al. Lenalidomide (LEN) maintenance (MNTC) after high-dose melphalan and autologous stem cell transplant (ASCT) in multiple myeloma (MM): a meta-analysis (MA) of overall survival (OS). Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.