The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between multiple disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histo-pathological, and radiological disease markers. At presentation and during follow-up, specific tests are needed for exact disease characterization and correct diagnosis. These tests can also serve as prognostic markers and are useful for follow-up of a myeloma patient. In addition, molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches allow to acquire additional prognostic information on patients9 long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group here updated their guidelines on different diagnostic recommendations, which should be of value to allow their appropriate use both at diagnosis and follow-up.

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended.

Autologous hematopoietic cell transplantation (AHCT) is a standard of care in multiple myeloma (MM) patients aged <65 years. To understand age-related trends in utilisation and outcome of AHCT, we analysed 53 675 MM patients who underwent a first AHCT in 31 European countries between 1991 and 2010. The number of patients undergoing AHCT increased for all age groups (<40, 40–49, 50–59, 60–64, 65–69 and ⩾70 years) throughout the observation period. The highest increase was observed for patients aged ⩾65 years, who accounted for 3% of AHCTs in 1991–1995 and for 18.8% of AHCTs in 2006–2010. Risk factors associated with survival over the entire observation period (P<0.001) were calendar period, remission status at AHCT, gender, disease duration before AHCT and age. Survival improved considerably more in older than in younger patients in recent years. In 2006–2010, median 2- and 5-year post-transplant survival ranged from 85.9 and 61.5% in patients <40 years to 80.2 and 49.7% in those ⩾70 years. All-cause day-100 mortality decreased throughout the observation period to ⩽2.4% for all age groups in 2006–2010. The results of this study demonstrate increased utilisation and safety of AHCT with improved post-transplant survival particularly in elderly MM patients in recent years in Europe.