Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial
Open Access
- 30 June 2021
- journal article
- research article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 106 (7), 1957-1967
- https://doi.org/10.3324/haematol.2020.247130
Abstract
The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unre-solved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalido-mide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was adminis-tered before autologous stem-cell transplantation to patients with a subopti-mal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free sur-vival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance.Keywords
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