The Clinical Outcomes of Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: A Nationwide Registry Study of the Korean Multiple Myeloma Working Party (KMMWP)

Background : Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited reported data on its efficacy and safety in the real clinical practice. The purpose of this study was estimate necessity of RD chemotherapy for improving survival in RRMM in real clinical fields.

Methods : Data from patients at twenty two university hospitals in South Korea between December 2012 and Oct 2016 were collected retrospectively. Clinical and laboratory data were collected retrospectively by review of medical records. The study protocol was approved by the institutional review board of each participating hospital. Patient characteristics were described at the status before lenalidomide treatment start except for cytogenetics and international staging systems, which were described from the data established at the time of diagnosis. The progression free survival (PFS) was defined duration from the date of starting RD chemotherapy to the date of disease progression, relapse, or death from any causes. OS was calculated from the start of lenalidomide treatment to the date of death or the date of last follow-up. Cox proportional hazard regression model was used for a multivariate analysis for PFS and OS. Prognostic factors significant in univariate analysis for PFS or OS were entered for multivariate analysis.

Results : The median age of the 527 patients was 66 years (range, 30-109 years) and the male to female ratio was 1.22:1.0. Patients previously were exposed to bortezomib only (40.0 %), both thalidomide and bortezomib (40.1%), and patients who had prior autologous stem cell transplantation were 37.2 %. Median number of cycles of RD were 6 (range, 1-37). The response rates were following: CR or stringent CR (sCR) in 84 (15.4%), VGPR in 106 (20.1%),PR in 166 (31.5%), MR in 24 (4.6%) and < MR in 101 (19.2%). Overall response rates (≥PR (partial response)) rate was 74.0 %. The differences of 2-year PFS of patients with achieved VGPR or more than VGPR and less than VGPR were 47.9% vs 30.2%, p<0.001. The 2-year OS were 66.4% vs 43.1%, p<0.001. The differences of 2-year PFS of patients treated with RD less than 6 cycles and 6 cycles or more than 6 cycles were 16.6% vs 53.4%, p<0.001. The 2-year OS were 26.2% vs 70.3%, p<0.001. In multivariate analysis, these two prognostic factors were shown significant prolonged survival (PFS; p=0.031 and p<0.001, OS; 0.017 and p<0.001). Adverse events of more than grade 2 were reported. Hematologic toxicities including cytopenia was observed only in 9.7 % of patients, infections including pneumonia in 15.1%, fatigue in 14.8%, skin rash in 7.0% and thrombosis in 3.0 %.

Conclusions : Our study confirms that RD is effective and safe in RRMM. It produces prolonged survival especially in patients who received more than 6 cycles and achieved more than PR response. Toxicities from RD were tolerable for RRMM patients.