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Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.

Treatments for myeloma have expanded in the last decade, but it is not clear if the introduction of novel therapies and the increased use of high-dose therapy have translated into better outcome for patients with myeloma. We examined the outcome of 2 groups of patients seen at a single institution, one from time of diagnosis and the other from the time of relapse, to examine the survival trends over time. Among 387 patients relapsing after stemcell transplantation, a clear improvement in overall survival from the time of relapse was seen, with those relapsing after 2000 having a median overall survival of 23.9 versus 11.8 months (P < .001) for those who relapsed prior to this date. This improvement was independent of other prognostic factors. Patients treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 vs 14.8 months; P < .001). In a larger group of 2981 patients with newly diagnosed myeloma, those diagnosed in the last decade had a 50% improvement in overall survival (44.8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis. IntroductionMultiple myeloma (MM), a neoplasm of plasma cells, affects 1 to 5 per 100 000 individuals each year worldwide with a higher incidence in the West. 1 It is the second most common hematologic malignancy in the United States, and it is estimated that there will be 19 900 new diagnoses and 10 790 deaths due to myeloma in 2007. 2 The median survival of patients with MM was less than a year before introduction of alkylating agents, and the introduction of melphalan in the 1960s resulted in improved survival. 3,4 A timeline of major therapeutic advances in multiple myeloma is outlined in Table 1. In the 1980s, introduction of high-dose chemotherapy and stem-cell rescue (ASCT) was introduced, and randomized trials since have demonstrated a survival advantage for this modality compared with conventional chemotherapy (CCT). [5][6][7] The introduction of thalidomide represented a major milestone in the treatment of myeloma, and the subsequent availability of its analog lenalidomide and the proteasome inhibitor bortezomib have expanded the therapeutic armamentarium for myeloma. [8][9][10][11][12] Incorporation of these novel agents has resulted in a paradigm shift in the treatment of myeloma, with their use earlier in the disease course. 13 While the new drugs have allowed successful salvage of relapsed disease, it is not clear if the survival of patients has improved during the last few years. We examined patients seen at our institution over a 36-year period to determine whether there has been an improvement in survival of myeloma patients seen during this time period. MethodsWe examined 2 cohorts of patients seen at Mayo Clinic with a diagnosis of MM. The first cohort consisted of 387 patients who were examined for potential improvement in survival following first relapse after ASCT. These patients we...

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumor genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the dataset. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signaling was suggested by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.