Plasmacytoma

The Myeloma XI study 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 based on International Myeloma Working Group response criteria) to allocate induction intensification treatment; and at the completion of induction and intensification or autologous haemopoietic stem cell transplantation (where applicable) to allocate maintenance treatment. This Article reports the results of the randomisation to induction intensification treatment. Results of the induction and maintenance randomisations have been,⁸ (link) or will, be presented elsewhere. The trial recruited from 110 National Health Service hospitals in England, Wales, and Scotland (appendix p 15).Figure 1

Trial profile of Myeloma XI

Area highlighted is the CVD randomisation reported in this manuscript. C=cyclophosphamide. D=dexamethasone. R=lenalidomide. T=thalidomide. V=bortezomib.

Eligible patients for the overall study were at least 18 years of age and had newly diagnosed multiple myeloma, based on paraprotein in serum or urine, bone marrow clonal plasma cells or plasmacytoma, and myeloma-related symptoms or organ or tissue impairment. Eligible patients for the intensification randomisation reported here additionally had to have completed their assigned induction therapy as per protocol (cyclophosphamide, thalidomide, and dexamethasone or cyclophosphamide, lenalidomide, and dexamethasone) and achieved a partial or minimal response. Patients were excluded at trial entry if they had other previous or concurrent malignancies, including myelodysplastic syndromes, previous treatment for myeloma (excluding local radiotherapy, bisphosphonates, and corticosteroids), grade 2 or higher 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), or active or previous hepatitis C infection. 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 done according to the Declaration of Helsinki and the principles of Good Clinical Practice as espoused in the Medicines for Human Use (Clinical Trials) Regulations. The study was not originally designed as an adaptive trial however good recruitment and the emergence of data on novel combinations led to trial adaptation. These changes were proposed by the Trial Management Group and approved by the independent Data Monitoring and Ethics Committee and Trial Steering Committee. The final study protocol is in the appendix (p 19). All patients provided written informed consent.

Participant variables included sex (male/female), race (White/Black/others), age at diagnosis (< 60 years/≥ 60 years) (15 (link)), year of diagnosis (2007–2011/2012–2016), marital status (married/unmarried), pathological type (DLBCL/others), surgery (yes/no evidence), radiotherapy (yes/no evidence), and chemotherapy (yes/no evidence) (9 (link)). Other races included American Indian/Alaska Native and Asian/Pacific Islander. Other pathological types included precursor non-Hodgkin B-cell lymphoma; chronic/small lymphocytic leukemia/lymphoma; mantle-cell lymphoma; lymphoplasmacytic lymphoma; intravascular large B-cell lymphoma; Burkitt lymphoma/leukemia; extranodal margin zone lymphoma (MZL); mucosa-associated lymphoid tissue (MALT) cell lymphoma; follicular lymphoma; plasmacytoma; multiple myeloma/plasma-cell leukemia; non-Hodgkin 1ymphoma, B-cell, not otherwise specified (NOS); peripheral T-cell lymphoma, NOS; anaplastic large cell lymphoma, T-/null-cell lymphoma; adult T-cell leukemia/lymphoma; and non-Hodgkin lymphoma, NOS, unknown lineage (12 ).
NCSS was defined as the period from the date of diagnosis to death from non-cancer-specific causes (5 (link)). Follow-up time was calculated as the period from the date of diagnosis with PCNSL until the date of death or last follow-up on December 31, 2016.

In total, 159 consecutive patients with MM, 120 with newly diagnosed MM (NDMM), 25 with relapsed/refractory MM, 14 with smouldering MM (SMM), 62 with MGUS, and 31 with lymphoma without BM infiltration were enrolled in this study between January 2011 and January 2021. The demographics of MM patients are summarized in Table 2. BM aspirate samples and four biopsied extramedullary plasmacytoma samples were obtained upon diagnosis after obtaining informed consent from each patient. This study was approved by the Institutional Review Board of Gunma University Hospital under the guidelines of the Declaration of Helsinki (IRB 810 and 1295).