The Myeloma XI was a phase 3, open-label, randomised, adaptive design trial with three randomisation stages (figure 1 ). There were three potential randomisations in the study: at trial entry for all patients to allocate induction treatment separately for those considered eligible or ineligible for transplantation; after induction treatment for those patients with a suboptimal response to treatment (minimal or partial response) to allocate induction intensification; and at the completion of induction and intensification or autologous stem-cell transplantation (where applicable) to allocate maintenance treatment. This report is concerned with the results of the randomisation to maintenance treatment. Results of the induction intensification randomisations will be presented elsewhere. The trial was done at 110 National Health Service hospitals in England, Wales, and Scotland (appendix p 2 ).![]()
appendix (p 34) . Patients aged at least 18 years and who had symptomatic multiple myeloma or non-secretory multiple myeloma based on bone marrow clonal plasma cells, organ or tissue impairment considered by the clinician to be myeloma related, or paraprotein (M-protein) in serum or urine were eligible for the initial randomisation. Exclusion criteria for the initial randomisation included previous or concurrent malignancies, including myelodysplastic syndromes; previous treatment for myeloma (except local radiotherapy, bisphosphonates, and corticosteroids); grade 2 or worse peripheral neuropathy, acute renal failure (unresponsive to up to 72 h of rehydration, characterised by creatinine >500 μmol/L or urine output <400 mL per day, or requiring dialysis); and active or previous hepatitis C infection.
Patients who were young and fit to tolerate autologous stem-cell transplantation (transplantation eligible) entered the intensive treatment pathway. Older and less fit patients (transplantation ineligible) entered the non-intensive treatment pathway. Strict age limits were deliberately avoided so that fit, older patients could receive intensive therapy and undergo autologous stem-cell transplantation. However, generally, patients aged 60 years or younger entered the intensive (younger, fitter) pathway; those aged 70 years or older entered the non-intensive (older, less fit) pathway; and those aged 61–69 years were eligible for either intensive or non-intensive therapy. The decision of treatment pathway was made on an individual patient basis, taking into account Eastern Cooperative Oncology Group performance status, clinician judgment, and patient preference.
For the maintenance therapy randomisation, eligible patients were those who completed their assigned induction therapy according to the protocol (a minimum of four cycles of cyclophosphamide, thalidomide, and dexamethasone [CTD]; cyclophosphamide, lenalidomide, and dexamethasone [CRD]; or carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone [KCRD] in the intensive pathway, or a minimum of six cycles of attenuated CTD or attenuated CRD in the non-intensive pathway), and had achieved at least a minimal response and received at least 100 mg/m2 melphalan if assigned to intensive treatment.
The study was approved by the national ethics review board (National Research Ethics Service, London, UK), institutional review boards of the participating centres, and the competent regulatory authority (Medicines and Healthcare Products Regulatory Agency, London, UK), and was undertaken according to the Declaration of Helsinki and the principles of Good Clinical Practice as espoused in the Medicines for Human Use (Clinical Trials) Regulations. All patients provided written informed consent. The study is closed for accrual, but follow-up continues for planned long-term analysis.
Trial profile
*Randomisation occurred between May 26, 2010, and April 20, 2016. †Randomisation occurred between Jan 13, 2011, and Aug 11, 2017. ‡Censored for progression-free survival analysis.
Patients who were young and fit to tolerate autologous stem-cell transplantation (transplantation eligible) entered the intensive treatment pathway. Older and less fit patients (transplantation ineligible) entered the non-intensive treatment pathway. Strict age limits were deliberately avoided so that fit, older patients could receive intensive therapy and undergo autologous stem-cell transplantation. However, generally, patients aged 60 years or younger entered the intensive (younger, fitter) pathway; those aged 70 years or older entered the non-intensive (older, less fit) pathway; and those aged 61–69 years were eligible for either intensive or non-intensive therapy. The decision of treatment pathway was made on an individual patient basis, taking into account Eastern Cooperative Oncology Group performance status, clinician judgment, and patient preference.
For the maintenance therapy randomisation, eligible patients were those who completed their assigned induction therapy according to the protocol (a minimum of four cycles of cyclophosphamide, thalidomide, and dexamethasone [CTD]; cyclophosphamide, lenalidomide, and dexamethasone [CRD]; or carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone [KCRD] in the intensive pathway, or a minimum of six cycles of attenuated CTD or attenuated CRD in the non-intensive pathway), and had achieved at least a minimal response and received at least 100 mg/m2 melphalan if assigned to intensive treatment.
The study was approved by the national ethics review board (National Research Ethics Service, London, UK), institutional review boards of the participating centres, and the competent regulatory authority (Medicines and Healthcare Products Regulatory Agency, London, UK), and was undertaken according to the Declaration of Helsinki and the principles of Good Clinical Practice as espoused in the Medicines for Human Use (Clinical Trials) Regulations. All patients provided written informed consent. The study is closed for accrual, but follow-up continues for planned long-term analysis.
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