CHICAGO–Compared with placebo or no maintenance therapy, maintenance therapy with lenalidomide lengthened overall survival (OS) for patients with multiple myeloma (MM) who had undergone autologous hematopoietic cell transplantation (AHCT), according to a meta-analysis presented by Phillip McCarthy, MD, from the Roswell Park Cancer Institute in Buffalo, New York, at the 2016 American Society of Clinical Oncology Annual Meeting.
“Several studies demonstrate that lenalidomide maintenance post-transplant reduces the risk of disease progression or death in patients with MM by approximately 50 percent,” Dr. McCarthy and colleagues wrote. “However, these studies were not powered for OS.”
The researchers conducted a meta-analysis of randomized controlled trials that evaluated maintenance lenalidomide in MM patients who had undergone AHCT. Trials were included in the analysis if they had patient-level data available, used a control arm, and analyzed efficacy in patients with newly diagnosed MM. Three trials met inclusion criteria:
- IFM 2005-02: a phase III, double-blind, multi-center trial that compared lenalidomide (10 mg/day for 3 months, increased to 15 mg/day if tolerated) with placebo in patients <65 years
- CALGB 100104: a phase III, double-blind trial that compared lenalidomide (10 mg/day) with placebo in patients <71 years
- GIMEMA RV-209: a phase III, open-label, multi-center trial that compared high-dose melphalan (200 mg/m2) with a combination of melphalan, prednisone, and lenalidomide (10 mg/day given 21 days in every 28-day cycle) in patients <65 years
The three randomized controlled trials included a total of 1,209 patients: 605 patients received lenalidomide, and 604 patients received maintenance therapy with a placebo or no maintenance therapy (control group). “Baseline characteristics were generally well balanced in the pooled data,” the authors noted. “A cut-off date of March 2015 enabled sufficient OS events to test treatment effect.”
After induction therapy, 82 percent of patients underwent single AHCT and 18 percent underwent tandem AHCT. Fifty-five percent of patients achieved a very good partial response (VGPR) or a complete response (CR) after transplant.
During a median follow-up of 6.6 years, the researchers learned that 491 patients (41% of the entire study group) had died during this time period.
Patients in the lenalidomide maintenance group had significantly longer OS than those in the control group: median OS was not reached in the lenalidomide group, versus 86 months in the control group (hazard ratio [HR] = 0.74; 95% CI 0.62-0.89; p=0.001).
The OS benefit with lenalidomide was also evident through seven years of follow-up, Dr. McCarthy and colleagues noted. For lenalidomide versus control, rates of OS reached:
- 71% vs. 66% at 5 years
- 65% vs. 58% at 6 years
- 62% vs. 50% at 7 years (p=0.001 for all)
Patients who achieved a partial response (PR) or lower after transplant benefitted from lenalidomide maintenance compared with controls (HR=0.86; 95% CI 0.65-1.15), as did patients who achieved VGPR or CR (HR=0.70; 95% CI 0.54-0.90).
“This large meta-analysis demonstrated that lenalidomide maintenance significantly prolonged overall survival versus control post-AHCT, including in patients who achieved CR,” the authors wrote, “demonstrating benefit in patients in all response categories.”
The risk of developing a hematologic secondary primary malignancy (SPM) post-AHCT was higher in the lenalidomide group (HR=2.03; 95% CI 1.14-3.61; p value not provided), however, Dr. McCarthy noted, “[the OS benefit] outweighs the risk of developing a SPM. … Lenalidomide maintenance is feasible for long-term disease control after [AHCT] and can be considered a standard of care.”
Although the authors determined that the OS benefit was “generally consistent across subgroups,” they observed significant differences across trials on a heterogeneity test (p=0.047). The heterogeneity could be explained by different induction regimens and pre-transplant consolidation therapies used in the individual trials, or differences in types and frequency of second-line therapies, Dr. McCarthy explained.
Whether patients’ baseline characteristics, disease characteristics, or second-line therapy (which was used in the IFM 2005-02 and CLGB 100104 trials) affected survival outcomes will need to be explored in future analyses.
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). Abstract #8001. Presented at the 2016 ASCO Annual Meeting, June 3, 2016; Chicago, IL.