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Plasma Cell Disorders
Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial
Ferrata Storti Foundation
Haematologica 2021 Volume 106(7):1957-1967
Graham H. Jackson,1 Faith E. Davies,2 Charlotte Pawlyn,3 David A. Cairns,4 Alina Striha,4 Corinne Collett,4 Anna Waterhouse,4 John R. Jones,5
Bhuvan Kishore,6 Mamta Garg,7 Cathy D. Williams,8 Kamaraj Karunanithi,9 Jindriska Lindsay,10 David Allotey,11 Salim Shafeek,12 Matthew W. Jenner,13 Gordon Cook,14 Nigel H. Russell,8 Martin F. Kaiser,3 Mark T. Drayson,15
Roger G. Owen,16 Walter M. Gregory4 and Gareth J. Morgan2 for the UK NCRI Haematological Oncology Clinical Studies Group
1Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK; 2Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA; 3The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK; 4Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK; 5King’s College Hospital NHS Foundation Trust, London, UK; 6Heart of England NHS Foundation Trust, Birmingham, UK; 7Leicester Royal Infirmary, Leicester, UK; 8Centre for Clinical Haematology, Nottingham University Hospital, Nottingham, UK; 9University Hospital of North Midlands, Stoke-on-Trent, UK; 10East Kent Hospitals University NHS Foundation Trust, Canterbury, UK; 11Derby Teaching Hospitals NHS Foundation Trust, Derby, UK; 12Worcestershire Acute Hospitals NHS Trust, Worcester, UK; 13University Hospital Southampton NHS Foundation Trust, Southampton, UK; 14Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK; 15Clinical Immunology, School of Immunity and Infection, University of Birmingham, Birmingham, UK and 16St James's University Hospital, Haematological Malignancy Diagnostic Service (HMDS), Leeds, UK
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. The trial was registered with the EU Clinical Trials Register (EudraCT 2009- 010956-93) and ISRCTN49407852.
Correspondence:
GRAHAM H. JACKSON
graham.jackson@newcastle.ac.uk
Received: January 20, 2020. Accepted: May 28, 2020. Pre-published: June 4, 2020.
https://doi.org/10.3324/haematol.2020.247130
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