Meta-analysis suggests that lenalidomide-carfilzomib may be the most effective maintenance treatment in patients with newly diagnosed multiple myeloma.
Eventual relapse and progression of newly diagnosed multiple myeloma (NDMM) is inevitable after induction and consolidation treatment. To prolong long-term survival in patients with MM, maintenance therapy has been extensively studied and investigated as it presumably enhances responses to initial treatment. There are many novel advances to maintenance treatment options that include immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies; however, the most appropriate regimen after induction therapy is still controversial. Yongjin Zhi and colleagues published a paper detailing results from a systematic review that aimed to identify the most effective maintenance treatment for NDMM patients.
A total of 19 trials with 11 treatments and 8337 patients were included in the analysis. All studies reported progression-free survival (PFS); however, 5 did not report overall survival (OS) data. Mean time to follow-up was 12.9 months to 4.1 years. There was no OS benefit compared to placebo observed for 6-month and 12-month OS in any trial. Overall, OS benefit was most significant over placebo with lenalidomide (odds ratio [OR], 1.61-1.99) and daratumumab (OR, 1.83-2.41). Lenalidomide improved 18-month, 24-month, 30-month, 36-month, 42-month, and 48-month survival, while daratumumab improved 36-month, 42-month, and 48-month survival and was comparable to lenalidomide. Trials showing significant improvement of PFS over placebo included lenalidomide-carfilzomib (OR, 3.19-6.95), lenalidomide-prednisone (OR, 2.62-4.44), bortezomib-thalidomide (OR, 2.48-3.64), daratumumab (OR, 2.0-2.98), lenalidomide (OR, 1.4-3.19), ixazomib (OR, 1.36-2.05), and thalidomide (OR, 1.5-1.86). Lenalidomide-carfilzomib was superior to lenalidomide alone (OR, 2.18-2.20), daratumumab (OR, 1.49-2.66), and ixazomib (OR, 2.75-3.57).
This study is the first network meta-analysis to compare relative efficacy of maintenance treatments in MM. Lenalidomide OS benefit occurs more rapidly than with daratumumab, and there was no OS benefit with other suggested regimens. Additionally, lenalidomide-carfilzomib showed a significant PFS benefit as early as 6 months and was associated with a greater benefit than with lenalidomide, daratumumab, or ixazomib. Although more head-to-head trials are necessary, this meta-analysis can support the use of lenalidomide as post–autologous stem-cell transplant maintenance therapy as standard of care with the possibility to incorporate carfilzomib considering adverse events and financial burden in clinical practice.
- Zhi Y, Bao S, Mao J, et al. Efficacy of maintenance treatment in patients with multiple myeloma: a systematic review and network meta-analysis. Hematology. 2022;27:1069-1088.