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Background: The aetiology of multiple myeloma (MM) is unknown but various environmental exposures are suspected as risk factors. We present the first paper analysing the geographical distribution of MM in Denmark at the municipal level to investigate variations that could be explained by environmental exposures. Methods: Patients diagnosed with MM in Denmark during 2005–2020 were identified from nationwide registries and grouped into the 98 Danish municipalities based on residence. The age‐ and sex‐standardised incidence rate (SIR) of each municipality was compared to the national incidence in a funnel plot with 95% control limits. Differences in SIRs of rural, suburban, and urban areas were evaluated with incidence rate ratios. Results: In total, 5243 MM patients were included. Overall, we found a heterogeneous geographical distribution of MM and a potential hotspot in southern Denmark. This hotspot contains three municipalities with SIRs above the 95% control limit assuming considerably higher rate of MM compared to the national incidence rate. A significant higher SIR was found in rural areas compared to urban areas. Conclusion: The geographical distribution of MM in Denmark indicates that the risk of developing MM depends on place of residence probably due to environmental factors. [ABSTRACT FROM AUTHOR]

Objective: We describe real‐world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). Method: First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005–2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. Results: We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high‐risk MM in a real‐ world‐population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. Conclusion: National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs. [ABSTRACT FROM AUTHOR]

Objective: We investigated the efficacy and safety of carfilzomib‐containing induction before salvage high‐dose melphalan with autologous stem‐cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods: This randomised, open‐label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re‐induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 → 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results: Median time to progression (TTP) after randomisation was 25.1 months (22.5‐NR) in the carfilzomib‐dexamethasone maintenance group and 16.7 months (14.4–21.8) in the control group (HR 0.46, 95% CI 0.30–0.71; P =.0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well‐tolerated with manageable toxicity. [ABSTRACT FROM AUTHOR]

Objectives: The Danish Myeloma Study Group initiated a randomized, placebo‐controlled, double‐blinded phase II study to investigate the efficacy of adding clarithromycin to cyclophosphamide‐bortezomib‐dexamethasone (VCD) induction therapy in transplant eligible, newly diagnosed multiple myeloma patients. The study was prematurely terminated due to severe complications, and no effect of adding clarithromycin was found. The aim of this study was to compare health‐related quality of life (HRQoL) between the two groups and to explore the coherence hereof with adverse event (AE) registration by clinicians. Methods: Patients completed three validated HRQoL questionnaires at inclusion, before cyclophosphamide priming, and two months after high‐dose therapy (HDT). The mean score difference was interpreted by clinically relevant differences between groups. Spearman's correlation analysis was used to compare patient‐reported toxicities with AEs. Results: Of 58 included patients, 55 participated in the HRQoL reporting. Before cyclophosphamide priming, patients in the clarithromycin group reported clinically relevant reduced HRQoL for eleven domains with persistent reduction in four domains two months after HDT. Poor correlation between patient‐reported toxicities and clinician‐reported AEs was observed. Conclusions: Despite the premature study termination, our data demonstrate impaired HRQoL when clarithromycin was added to the VCD regimen. We found clear underreporting of toxicities by clinicians. ClinicalTrials.gov number NCT02573935. [ABSTRACT FROM AUTHOR]

Several risk scores for disease progression in patients with smoldering multiple myeloma ( SMM) have been proposed; however, all have been developed using single-center registries. To examine risk factors for time to progression ( TTP) to multiple myeloma ( MM) for SMM, we analyzed a nationwide population-based cohort of 321 patients with newly diagnosed SMM registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥30 g/L and immunoparesis significantly influenced TTP ( HR 2.7, 95% CI (1.5;4.7), P = 0.001, and HR 3.3, 95% CI (1.4;7.8), P = 0.002, respectively). High free light chain ( FLC) ratio did not significantly influence TTP in our cohort. Therefore, our data do not support recent IMWG proposal of identifying patients with FLC ratio above 100 as having ultra high-risk of transformation to MM. Using only immunoparesis and M-protein ≥30 g/L, we created a scoring system to identify low-, intermediate-, and high-risk SMM. This first population-based study of patients with SMM confirms that an M-protein ≥30 g/L and immunoparesis remain important risk factors for progression to MM. [ABSTRACT FROM AUTHOR]

The article presents a population-based study of 348 myeloma patients undergoing autologous transplant. The researchers have tested functionally important polymorphisms in the P2RX7 and P2RY2 genes for association with risk of disease. Chi-square test or fisher's exact test, Kaplan-Meier method and log rank test, and cox proportional hazard analysis were used in the study.