Efficacy
The 1208 patients within the meta-analysis (605 in the lenalidomide maintenance group and 603 in placebo/observation group) had a median follow-up of 79.5 months and mean treatment duration of 28 months with lenalidomide maintenance and 22 months with placebo or observation. Pooled median PFS was 52.8 months in the lenalidomide group and 23.5 months in the placebo/observation group (HR 0.48, 95% CI 0.41-0.55). This improvement was confirmed in all included studies.
Figure 1: Kaplan-Meier estimates of PFS (A). Hazard ratios (HRs) for PFS by individual study (B).r
© Journal of Clinical Oncology 2017
OS was also improved, with median OS not being reached in the lenalidomide maintenance group but 86 months in the placebo/observation group (HR 0.75, 95% CI 0.63-0.90), representing a 25% risk reduction in risk of death. The 7-year survival rate was 62% with lenalidomide maintenance and 50% with placebo/observation.
Figure 2: Kaplan-Meier estimates of OSr
© Journal of Clinical Oncology 2017
1971 patients were randomised to Myeloma XI’s maintenance arm, with 1137 in the lenalidomide maintenance group and 834 in the observation group. With median follow-up after randomisation of 31 months, median PFS was 39 months with lenalidomide maintenance and 20 months with observation (HR 0.46, 95% CI 0.41-0.53). Median OS was not reached in either group and there was no difference between groups in OS (HR 0.87 95% CI 0.73-1.05). 40% of the lenalidomide group and 64% of the observation group had disease progression or died. Median duration of lenalidomide maintenance was 18 cycles.
Figure 3: Kaplan-Meier plots of progression-free survival (A) and overall survival (B) in the intention-to-treat populationr
© Lancet Oncology 2019
Notably, in a pre-specified analysis by transplant eligibility in Myeloma XI, transplant eligible patients received the most benefit from lenalidomide maintenance. Within the transplant eligible group, PFS was 57 months with lenalidomide and 30 months with observation (HR 0.48, 95% CI 0.40-0.58) but in transplant ineligible patients, PFS was 26 months with lenalidomide and 11 months with observation (HR 0.44, 95% CI 0.37-0.53).r Similarly, within the transplantation eligible group 3-year OS was 87.5% with lenalidomide and 80.2% with observation (HR 0.69, 95% CI 0.52-0.93) but there was no effect in the transplant ineligible group with 3-year OS of 66.8% with lenalidomide and 69.8% with observation (HR 1.02, 95% CI 0.80-1.29).
Figure 4: Kaplan-Meier plot of progression-free survival 2 in transplantation-eligible patients (A) and transplantation-ineligible patients (B)r
© Lancet Oncology 2019
Myeloma XIr also included a pooled analysis of all available data for lenalidomide maintenance post SCT for newly diagnosed MM, including other papers (5), (7) and (8). With the addition of the Myeloma XI data, meta-analysis of all published lenalidomide maintenance after autologous stem-cell transplantation data ( N = 3179 patients overall) was undertaken and showed OS benefit for post-AutoSCT lenalidomide (compared to observation) with HR 0.72 (0.56 – 0.91).
More contemporary, ‘real-world’ datar exists demonstrating deepening of responses over time in patients receiving lenalidomide maintenance post transplantation. This retrospective ‘real-world’ analysis included N = 139 patients treated in whom minimal residual disease (MRD) data (sensitivity at least 10-4) were known (Flow cytometry or Next-generation sequencing). Lenalidomide maintenance correlated with an increased depth of the disease response, with 38.1% of patients achieving maximal response during maintenance, and 34.3% of patients who were MRD positive after induction treatment achieved MRD-negative status during maintenance and ultimately had improved PFS. These results support the role of maintenance therapy, to increase depth of response to front-line treatment, which has been shown previously to correlate with improved survival.
Figure 5: Deepening responses with duration lenalidomide exposure post SCTr
©Blood Adv 2020