Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify MM patients. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase Fluorescence In Situ Hybridization (iFISH) after CD138 plasma cells purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Methods Clinical and laboratory data from 4445 NDMM patients enrolled in eleven international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3060/4445 patients. We defined three groups: revised ISS (R-ISS) I (N=871), including ISS I (serum β2-microglobulin level <3.5mg/L and serum albumin level ≥3.5g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)] and normal LDH level (below the upper limit of normal range); R-ISS III (N=295), including ISS III (serum β2-microglobulin level >5.5mg/L) and high-risk CA or high LDH level; R-ISS II (N=1894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS was 55%, 36% and 24%, respectively. Conclusions The R-ISS is a simple and powerful prognostic staging system and we recommend its use in future clinical studies to stratify NDMM patients effectively with respect to the relative risk to their survival.

Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions. Much progress has been made over the past decade in the understanding of disease biology and individualized treatment approaches. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have joined the traditional armamentarium (corticosteroids, alkylating agents and anthracyclines) and, along with high-dose therapy and autologous haemopoietic stem cell transplantation, have led to deeper and durable clinical responses. Indeed, an increasing proportion of patients are achieving lasting remissions, raising the possibility of cure for this disease. Success will probably depend on using combinations of effective agents and treating patients in the early stages of disease, such as patients with smouldering multiple myeloma.

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.

AperTO -Archivio Istituzionale Open Access dell'Università di TorinoChemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial / Gay, Francesca; Oliva, Stefania; Petrucci, Maria Teresa; Conticello, Concetta; Catalano, Lucio; Corradini, Paolo; Siniscalchi, Agostina; Magarotto, Valeria; Pour, Ludk; Carella, Angelo; Malfitano, Alessandra; Petrò, Daniela; Evangelista, Andrea; Spada, Stefano; Pescosta, Norbert; Omedè, Paola; Campbell, Philip; Liberati, Anna Marina; Offidani, Massimo; Ria, Roberto; Pulini, Stefano; Patriarca, Francesca; Hajek, Roman; Spencer, Andrew; Boccadoro, Mario; Palumbo, Antonio. -In: LANCET ONCOLOGY. -ISSN 1470-ISSN -2045-ISSN . -16:16(2015, pp. 1617-1629. Original Citation:Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial This is an author version of the contribution published on:Questa è la versione dell'autore dell'opera: [Lancet Oncol. 2015 Dec;16(16):1617-29. doi: 10.1016/S1470-2045 Background. High-dose melphalan plus autologous stem-cell transplantation (MEL200-