Results of a retrospective, observational study of patients with newly diagnosed multiple myeloma receiving maintenance lenalidomide therapy in real-world clinical practice demonstrated the benefit of this approach in increasing the depth of response to induction/consolidation therapy. These findings were reported in Blood Advances.1
Maintenance therapy with lenalidomide, an oral, immunomodulatory agent, has been approved by the US Food and Drug Administration (FDA), as well as other regulatory agencies, as maintenance therapy for the treatment of patients with newly diagnosed multiple myeloma based on the findings of large, randomized phase 3 studies showing increased progression-free survival (PFS) and overall survival (OS) in patients receiving lenalidomide in the maintenance setting compared with no maintenance treatment.2 Nevertheless, information on the impact of lenalidomide maintenance therapy on the depth of response — as well as the association between depth of response and prognosis — have not been well explored in this setting.
Included in this study were patients with newly diagnosed multiple myeloma treated with first-line lenalidomide maintenance therapy at 1 of 3 health centers between 2010 and 2018 for whom serial data on minimal residual disease (MRD) status, assessed using either next-generation sequencing of immunoglobulin genes or multiparametric flow cytometry, were available.
Assessments of MRD were performed prior to initiation of maintenance therapy and/or following achievement of complete response (CR), and then annually until a sustained negative MRD status was confirmed. Data on the MRD status of 387 bone marrow samples from 139 patients, along with other clinical, biological, and demographic information for this patient cohort, were evaluated in this study.
For the overall patient cohort, median age was 60 years, the median duration of maintenance therapy was 21 months, median PFS was 61 months, and 5-year OS was 82.6%.
Prior to the initiation of maintenance therapy, 45 patients (32.4%) in the overall cohort had not achieved a CR, and only 37 (26.6%) had achieved both a CR and MRD-negative status. However, at maximal response during maintenance therapy, the percentages of patients in the former and latter categories were 12.9% and 51.8%, respectively, showing that 38.1% of patients achieved maximal response during maintenance therapy,
Moreover, more than one-third of those with MRD-positive disease prior to initiation of maintenance therapy achieved a MRD-negative status while receiving lenalidomide maintenance therapy, with a median time to achievement of MRD-negative status of 18.5 months.
Notably, while achievement of MRD-negative status at maximal response during or after maintenance therapy was associated with improved PFS vs not (P =.011), there was no significant difference in the PFS of patients who achieved MRD-negative disease prior to initiation of, vs during, maintenance therapy (P =.34). In addition, for the subgroup achieving a sustained MRD-negative status during maintenance therapy, 4-year PFS rates were approximately 75% regardless of whether treatment was stopped or continued at confirmation of MRD-negativity.
Furthermore, results of an MRD kinetics analysis of the 52 patients with MRD-positive disease at the start of maintenance therapy showed that, over the course of treatment, 15 patients had no significant reduction in MRD level, 25 patients achieved MRD-negativity, and 12 patients exhibited decreasing MRD levels over time without achieving a MRD-negative status. A comparison of PFS in the latter 2 groups of patients showed no significant difference (P =.513).
“That there was no difference in PFS between this group of patients with favorable kinetics without immunophenotypic and molecular remission and those who ultimately obtained MRD negativity is encouraging, as well as surprising,” the study authors commented.
“We believe this finding supports the importance of prolonging lenalidomide therapy for as long as possible in patients who are MRD positive,” the study authors further noted.
Regarding the safety of lenalidomide maintenance therapy, 22.3% of patients in the study cohort discontinued treatment due to toxicity. In addition, 27.8% of patients underwent lenalidomide dose reductions, although they were not significantly associated with PFS (P =.894) or achievement of a MRD-negative status (P =.498).
In their concluding remarks, the study authors commented that “these results support the role of maintenance therapy, not only to sustain, but also to increase the depth of disease response with a PFS benefit. In addition, MRD monitoring during maintenance identifies patients with better prognosis and may help in their clinical management.”
- Alonso R, Cedena M-T, Wong S, et al. Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma [published online May 26, 2020]. Blood Adv. doi: 10.1182/bloodadvances.2020001508
- Lenalidomide (Revlimid®) [package insert]. Summit, NJ: Celgene Corporation: 2019.