VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.

In a recent phase 3 trial, bortezomibmelphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this posthoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P ‫؍‬ .54). The complete response rate was 30% in the onceweekly and 35% in the twice-weekly group (P ‫؍‬ .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P ‫؍‬ .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179. (Blood. 2010;116(23): 4745-4753)

Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma (MM) but is associated with an increased risk of venous thromboembolism (VTE

Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatmentrelated side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomibthalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials MP. 11,12 In patients aged 75 years or over, the efficacy of VMP was less evident: the 3-year OS was shorter in comparison with patients aged under 75 years (55% vs. 74%). The incidence of any grade 3-4 AEs was 91% and bortezomib discontinuation rate due to AEs was 34%. Both VMP and MPT are now considered the new standards of care for newly diagnosed MM patients aged 65 years or over. Recently, the combination of bortezomib and thalidomide with or without alkylating agents has shown to be highly effective. 13,14 The weekly administration of bortezomib reduced the incidence of AEs, especially peripheral neuropathy and gastrointestinal toxicity, without affecting efficacy.13,14 Nevertheless, outcome was mainly improved for patients aged under 75 years, while limited advantage was reported in patients aged 75 years or over.14 These data lead to the question as to whether less toxicity may translate into more efficacy, especially in unfit elderly patients.In this meta-analysis of individual patient data from 4 randomized trials, we assessed the influence of age, organ damage, development of treatment-related AEs and drug discontinuation as predictive factors of outcome in elderly newly diagnosed MM patients receiving MP, MPT, VMP, or bortezomib and thalidomide combination (bortezomib, thalidomide and prednisone [VTP] or bortezomib, melphalan, prednisone and thalidomide [VMPT]). Design and Methods Study design and treatmentsPa...

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.