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The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.

Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).

The stellar evolution code YREC is outlined with emphasis on its applications to helio- and asteroseismology. The procedure for calculating calibrated solar and stellar models is described. Other features of the code such as a non-local treatment of convective core overshoot, and the implementation of a parametrized description of turbulence in stellar models, are considered in some detail. The code has been extensively used for other astrophysical applications, some of which are briefly mentioned at the end of the paper., Comment: 10 pages, 2 figures, ApSS accepted

The stellar evolution code YREC is outlined with emphasis on its applications to helio- and asteroseismology. The procedure for calculating calibrated solar and stellar models is described. Other features of the code such as a non-local treatment of convective core overshoot, and the implementation of a parametrized description of turbulence in stellar models, are considered in some detail. The code has been extensively used for other astrophysical applications, some of which are briefly mentioned at the end of the paper., Comment: 10 pages, 2 figures, ApSS accepted

The stellar evolution code YREC is outlined with emphasis on its applications to helio- and asteroseismology. The procedure for calculating calibrated solar and stellar models is described. Other features of the code such as a non-local treatment of convective core overshoot, and the implementation of a parametrized description of turbulence in stellar models, are considered in some detail. The code has been extensively used for other astrophysical applications, some of which are briefly mentioned at the end of the paper., Comment: 10 pages, 2 figures, ApSS accepted

We present detailed evolutionary calculations focused on the evolution of intermediate mass stars with 3 Msun < M < 9 Msun of metallicity typical of the Large Magellanic Cloud (LMC), i.e. Z=0.008. We compare carefully the models calculated by adopting a diffusive scheme for chemical mixing, in which nuclear burning and mixing are self-consistently coupled, while the eddy velocities beyond the formal convective core boundary are treated to decay exponentially, and those calculated with the traditional instantaneous mixing approximation. We find that: i) the physical and chemical behaviour of the models during the H-burning phase is independent of the scheme used for the treatment of mixing inside the CNO burning core; ii) the duration of the He-burning phase relative to the MS phase is systematically longer in the diffusive models, due to a slower redistribution of helium to the core from the outer layers; iii) the fraction of time spent in the blue part of the clump, compared to the stay in the red, is larger in the diffusive models. The differences described in points ii) and iii) tend to vanish for M > Msun. In terms of the theoretical interpretation of an open cluster stellar population, the differences introduced by the use of a self-consistent scheme for mixing in the core with adjacent exponential decay are relevant for ages in the range 80 Myr < t < 200 Myr. These results are robust, since they are insensitive to the choice of the free-parameters regulating the extension of the extra-mixing region., Comment: 14 pages, 14 figure, accepted for publication on Astronomy & Astrophysics

We present detailed evolutionary calculations focused on the evolution of intermediate mass stars with 3 Msun < M < 9 Msun of metallicity typical of the Large Magellanic Cloud (LMC), i.e. Z=0.008. We compare carefully the models calculated by adopting a diffusive scheme for chemical mixing, in which nuclear burning and mixing are self-consistently coupled, while the eddy velocities beyond the formal convective core boundary are treated to decay exponentially, and those calculated with the traditional instantaneous mixing approximation. We find that: i) the physical and chemical behaviour of the models during the H-burning phase is independent of the scheme used for the treatment of mixing inside the CNO burning core; ii) the duration of the He-burning phase relative to the MS phase is systematically longer in the diffusive models, due to a slower redistribution of helium to the core from the outer layers; iii) the fraction of time spent in the blue part of the clump, compared to the stay in the red, is larger in the diffusive models. The differences described in points ii) and iii) tend to vanish for M > Msun. In terms of the theoretical interpretation of an open cluster stellar population, the differences introduced by the use of a self-consistent scheme for mixing in the core with adjacent exponential decay are relevant for ages in the range 80 Myr < t < 200 Myr. These results are robust, since they are insensitive to the choice of the free-parameters regulating the extension of the extra-mixing region., Comment: 14 pages, 14 figure, accepted for publication on Astronomy & Astrophysics

Time-dependent nuclear network calculations at constant temperature show that for zero-metal stars >= 20 Msun (i) beta-decay reactions and (ii) the 13N(p,gamma)14O reaction must be included. It is also shown that the nuclear timescale in these zero-metal stars is shorter than the mixing timescale and therefore the assumption of instantaneous mixing across convective regions is not fulfilled. We conclude that proper modeling of these processes may alter the evolution of massive zero-metal stars., Comment: 4 pages, 3 figures, submitted to A&A (Letter)

Time-dependent nuclear network calculations at constant temperature show that for zero-metal stars >= 20 Msun (i) beta-decay reactions and (ii) the 13N(p,gamma)14O reaction must be included. It is also shown that the nuclear timescale in these zero-metal stars is shorter than the mixing timescale and therefore the assumption of instantaneous mixing across convective regions is not fulfilled. We conclude that proper modeling of these processes may alter the evolution of massive zero-metal stars., Comment: 4 pages, 3 figures, submitted to A&A (Letter)