Risk-stratified continuous therapy significantly improved progression-free survival (PFS), overall survival (OS), and progression-free survival 2 (PFS2) in patients with high-risk multiple myeloma, according to a five-year follow-up analysis of the OPTIMUM trial published in The Lancet Oncology.
The findings suggest that "risk-stratified continuous combination treatment should be considered for patients with high-risk multiple myeloma and support access to diagnostic testing to identify transplant-eligible patients with newly diagnosed multiple myeloma who would benefit from risk-stratified treatment," wrote Martin F. Kaiser, MD, of the Institute of Cancer Research in London, UK, and colleagues.
The researchers conducted a prespecified analysis of the OPTIMUM study, a multicenter, externally controlled, phase 2 trial. The trial enrolled 108 adults (median age, 60 years; 60% men) with newly diagnosed plasma cell leukemia or high-risk multiple myeloma, defined as two or more high-risk cytogenetic abnormalities or a high-risk gene expression profile.
Participants received induction with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone, followed by autologous stem-cell transplantation and lenalidomide plus daratumumab maintenance. The control group included 120 molecularly matched patients from the Myeloma XI trial who received conventional induction therapy, autologous stem-cell transplantation, and lenalidomide maintenance.
The primary endpoint was 18-month PFS.
At a median follow-up of 70 months, PFS was significantly longer with risk-stratified continuous therapy compared with the Myeloma XI control. Median PFS was not reached in the extended therapy group versus 24.4 months in the control group (HR, 0.32; P < .0001). At 72 months, 53.8% of patients in the extended therapy group were progression-free compared with 17.6% in the control group.
OS was also significantly improved. Median OS was not reached in the extended therapy group versus 57.4 months in the control group (HR, 0.43; P < .0001). At 72 months, 69.1% of patients in the extended therapy group were alive compared with 42.5% in the control group.
Median PFS2 was not reached in the OPTIMUM group compared with 43.9 months in the external control group (HR, 0.26; P < .0001).
The survival benefit was consistent among patients with two or more high-risk cytogenetic abnormalities, a high-risk gene expression profile, or both. However, there was no discernible benefit among the seven patients in the OPTIMUM group who had three or more high-risk cytogenetic abnormalities compared with the 10 patients with the same risk features in the Myeloma XI control group.
Among patients with plasma cell leukemia, median PFS was 20.9 months, and median OS was 30.9 months.
The authors noted that the study's enrichment design may have limited generalizability, and safety data were not reported in the analysis.
https://www.medscape.com/viewarticle/994922