Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial
Abstract
The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) was administered before ASCT to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation (ASCT), eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (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.
Author
Jackson, Graham H
Davies, Faith E
Pawlyn, Charlotte
Cairns, David A
Striha, Alina
Collett, Corinne
Waterhouse, Anna
Jones, John R
Kishore, Bhuvan
Garg, Mamta
Williams, Cathy D
Karunanithi, Kamaraj
Lindsay, Jindriska
Allotey, David
Shafeek, Salim
Jenner, Matthew W
Cook, Gordon
Russell, Nigel H
Kaiser, Martin F
Drayson, Mark T
Owen, Roger G
Gregory, Walter M
Morgan, Gareth J
Clinical Studies Group, Uk Ncri Haematological Oncology
Davies, Faith E
Pawlyn, Charlotte
Cairns, David A
Striha, Alina
Collett, Corinne
Waterhouse, Anna
Jones, John R
Kishore, Bhuvan
Garg, Mamta
Williams, Cathy D
Karunanithi, Kamaraj
Lindsay, Jindriska
Allotey, David
Shafeek, Salim
Jenner, Matthew W
Cook, Gordon
Russell, Nigel H
Kaiser, Martin F
Drayson, Mark T
Owen, Roger G
Gregory, Walter M
Morgan, Gareth J
Clinical Studies Group, Uk Ncri Haematological Oncology
Citations
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Date
2021-07-01
Type
Article
Subject
Oncology. Pathology., Pharmacology, Microbiology. Immunology
Collections
Citation
Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Allotey D, Shafeek S, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Clinical Studies Group UNHO. Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial. Haematologica. 2021 Jul 1;106(7):1957-1967. doi: 10.3324/haematol.2020.247130
Journal / Source Title
Haematologica
DOI
10.3324/haematol.2020.247130
PMID
32499244
Publisher
Ferrata Storti Foundation
Publisher’s URL
http://www.haematologica.org