This International Myeloma Working Group consensus updates the disease defi nition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identifi cation of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfi l the criteria for the presence of myeloma-defi ning CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specifi c metrics that new biomarkers should meet for inclusion in the disease defi nition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any diff erences in outcome that might occur as a result of the new disease defi nition.

A B S T R A C T PurposeWe investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and MethodsIn all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stemcell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m 2 (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. ResultsComplete response (CR), including near CR, was superior after PAD induction (15% v 31%; P Ͻ .001) and bortezomib maintenance (34% v 49%; P Ͻ .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P ϭ .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P ϭ .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P ϭ .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P Ͻ .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P ϭ .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P ϭ .003). ConclusionBortezomib during induction and maintenance improves CR and achieves superior PFS and OS.

No abstract

We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1, 31%), and frail (score ≥2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506).

Multiple myeloma (MM) is a plasma cell neoplasm that accounts for 1%-1.8% of all cancers and is the second most common haematological malignancy with an estimated incidence in Europe of 4.5-6.0/100 000/year. Despite the significant improvement in patients' survival over the past 20 years, only 10%-15% of patients achieve or exceed expected survival compared with the matched general population. 1