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In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic.

Daratumumab is an integral part of the treatment of multiple myeloma (MM) but its real-world efficacy has only been described in small cohorts. MAMMOTH is the only large multi-center study that reported the outcomes of CD38-refractory MM. The present study includes a complete, Danish, nation-wide cohort of 635 MM patients who initiated treatment a daratumumab-containing index regimen (IR) prior to 1.1.2019, and describes the outcomes of 472 patients who discontinued their IR until 1.1.2021. Patients received a median of 3 lines of therapy (LOT) prior to the IR. The median time from diagnosis to discontinuation of the IR (T 0) was 4 years. At T 0, 73% of patients were quadruple drug class exposed (CE). The median overall survival (mOS) after T 0 was 12.2 months in the entire cohort, 15.3 months in double CE, 22.5 months in triple CE, 12.6 months in quadruple CE and 8.3 months in alkylator-bortezomib-carfilzomib-daratumumab-lenalidomide-pomalidomide-exposed patients. After T 0, 79%, 48%, 29%, 17%, 10% and 6% of patients received 1, 2, 3, 4, 5, 6 additional LOT, respectively, achieving overall response rates ranging from 44% to 11% and median time to next treatment (TNT) from 138 to 54 days. In the first subsequent LOT after T 0, 51% of patients were retreated with daratumumab. Despite the lack of benefit in terms response and TNT, daratumumab retreatment was associated with superior OS on multivariate analysis adjusting for age, previous transplantation, IR, drug class exposure at T 0, treating site, time from diagnosis to T 0 and presence of cytogenetic high-risk markers. Median OS was 24.6 months in patients retreated with and 11.3 months in patients treated without daratumumab (p Legends to Figure: A: Overall survival after T 0; B: Overall survival after T 0 by cytogenetic risk; C: Overall survival after T 0 by IR; D: Overall survival after T 0 by prior exposure. Abbreviations: T 0=time of discontinuation of the first daratumumab-containing line of therapy; IR=index regimen; high-risk=t(4;14), t(14;16) or del17p by FISH; D-mono=daratumumab monotherapy; D-bor=daratumumab-bortezomib-dexamethasone; D-len=daratumumab-lenalidomide-dexamethasone; D-other=daratumumab in other combinations; Double_CE=exposed to daratumumab and another class of drugs; Triple_CE=exposed to daratumumab and two other classes of drugs; Quadruple_CE=exposed to daratumumab and three other classes of drugs; ABCDLP-exposed=exposed to daratumumab, bortezomib, carfilzomib, lenalidomide and pomalidomide Figure 1 Figure 1. Disclosures Szabo: Takeda: Consultancy; Sanofi: Consultancy; Janssen: Consultancy.

Background: The severe, acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), leading to coronavirus-19 (COVID-19), was detected for the first time in Wuhan, China in December 2019. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the MM-related immunodeficiency (Glenthøj, A et al. PMID: 32939853). To some extent, the COVID-19 pandemic has changed standard of care towards extended use of oral regimens and limiting hospital visits (Terpos E et al.PMID: 32444866). We aimed to investigate the quality of life (QoL) of Danish patients with MM during the COVID-19 pandemic. We hypothesized that patients living alone and those under the age of 65 years, as a consequence of the pandemic, would experience impaired QoL due to social isolation and fear of infection with SARS-CoV-2. Methods: The Danish prospective, nation-wide, observational survey "Quality of life in Danish patients with multiple myeloma" (QoL-MM) (Nielsen LK et al. PMID: 30656677) framed our study. In QoL-MM, survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period. The following PRO questionnaires are used; the cancer-generic instrument of European Organisation for Research and Treatment of Cancer Quality of life (EORTC) QLQ-C30 (EORTC QLQ-C30), the Multiple Myeloma module QLQ-MY20 (EORTC QLQ-MY20), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey version 2 (SF12v2). In the present study, a subpopulation of the QoL-MM cohort was constructed, based on the response time of the questionnaires. QoL was compared using patient-reported outcome (PRO) data obtained before and during the COVID-19 pandemic at group level. In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The QoL data were analyzed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value Results: The study included 616 patients (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation, 9.2); 40% were females; 76% were married/cohabiting, and 24% single. Questionnaire completion rates during the investigated periods were between 96% and 97%. In total, 1,685 completed sets of questionnaires were included in the analyses. The patients reported no statistically significant and clinically relevant difference in QoL during the first and second waves of the COVID-19 pandemic, compared to one year earlier, see table 1. When analyzing the subpopulations, we found that patients below 65 years reported improved physical health summaries (p-value 0.016), decreased fatigue (p-value < 0.001), less insomnia (p-value 0.002) and improved role functioning (p-value Conclusion: As a group, Danish patients with MM did not report impaired QoL during the COVID-19 pandemic. In contrary, we observed improvements in some domains in patients below 65 years. Our observations indicate that the patients with MM have felt cared for and in good hands during the first and second waves of the COVID-19 pandemic. However, part of the reason for our finding of no negative impact on QoL by the pandemic could be that the questionnaires used were not developed to capture the impact of the pandemic on QoL. Importantly, our results suggest that QoL data collected in clinical trials during the pandemic allow interpretation without adjusting for the impact of the pandemic. Figure 1 Figure 1. Disclosures Redder: Janssen-Ciliag: Research Funding. Frederiksen: Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding.

Real world evidence is important since most patients cannot be included in randomized clinical trials (RCTs). In a nationwide, cohort of relapsed/refractory multiple myeloma patients treated with daratumumab (N = 635), we retrospective studied patients treated with carfilzomib (N = 251). Data were collected by audit of medical records. We compared characteristics of patients treated with carfilzomib before daratumumab (Car-Da; N = 150) and after daratumumab (Da-Car; N = 101) with those not treated with carfilzomib (N = 384). Furthermore, we examined effectiveness and safety of carfilzomib. The group of patients treated with carfilzomib differed from patients not treated with carfilzomib in the following parameters: They were younger, more were treated up-front with high dose melphalan and autologous stem cell transplantation (HDM-ASCT)and had relapse within 18 months thereafter, and more had high-risk cytogenetic abnormalities (CA) and amplification 1q (amp1q). In patients treated with Car-Da, 30.3% had high-risk CA and 30.1% had amp1q and in Da-Car it was 43.3% and 41%, respectively. In the Car-Da cohort, 34.4% experienced early relapse after HDM-ASCT versus 47.4% in the Da-Car cohort. The percentage of patients with very good partial remission was higher in patients treated with Car-Da compared to Da-Car (31.7% vs. 17.4%). The median duration of treatment and time to next treatment (TNT) of Car-Da/Da-Car were 4.6/4.3 months and 7.1/4.3 months and only a trend toward superior TNT for Car-Da was found (p = 0.06). Toxicity of carfilzomib was the same as reported in RCT. A similar poor TNT of daratumumab was found when used before (5.6 months) or after carfilzomib (4.9 months). In this cohort of patients with sequential treatment with carfilzomib and daratumumab or vice versa, a high percentage of patients were high-risk by CA, amp1q, and early relapse after HDM-ASCT. Outcome of Car-DA and outcome of Da-Car were equally poor. These patients should be considered for new promising treatment strategies.

In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.

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.

To describe use of bisphosphonates in newly diagnosed multiple myeloma patients in Denmark.Using data from the Danish National Multiple Myeloma Registry, we conducted a population-based cohort study. Among patients newly diagnosed with multiple myeloma from 2005 to 2015, we examined use of bisphosphonates at first- and at progression/second-line anti-myeloma treatment overall, by patient characteristics, and myeloma complications.Of 2947 patients starting first-line anti-myeloma treatment, 2207 patients (74.9%) received bisphosphonates. During a median follow-up of 27.6 (quartiles, 10.6-52.5) months, disease progression post-first-line treatment was recorded in 1546 patients, of whom 1065 (68.9%) were treated with bisphosphonates. Altogether, 80.9% of patients with and 37.6% of patients without myeloma bone disease were treated with bisphosphonates at first line and 73.0% and 42.7%, respectively, at progression/second line. Moreover, the proportion of patients treated with bisphosphonates decreased with increasing severity of renal impairment at first and at progression/second-line treatment.The proportion of patients treated with bisphosphonates as part of first- and second-line anti-myeloma treatment increased with presence of myeloma bone disease and decreased by presence and severity of renal impairment. Overall, 25% of newly diagnosed multiple myeloma patients had no record of bisphosphonate treatment, potentially indicating an unmet need.

Purpose The quality of patient-reported outcome (PRO) data can be compromised by non-response (NR) to scheduled questionnaires, particularly if reasons for NR are related to health problems, which may lead to unintended bias. The aim was to investigate whether electronic reminders and real-time monitoring improve PRO completion rate. Methods The population-based study “Quality of life in Danish multiple myeloma patients” is a longitudinal, multicentre study with consecutive inclusion of treatment-demanding newly diagnosed or relapsed patients with multiple myeloma. Education of study nurses in the avoidance of NR, electronic reminders, 7-day response windows and real-time monitoring of NR were integrated in the study. Patients complete PRO assessments at study entry and at 12 follow-up time points using electronic or paper questionnaires. The effect of the electronic reminders and real-time monitoring were investigated by comparison of proportions of completed questionnaires before and after each intervention. Results The first 271 included patients were analysed; of those, 249 (85%) chose electronic questionnaires. Eighty-four percent of the 1441 scheduled PRO assessments were completed within the 7-day response window and 11% after real-time monitoring, achieving a final PRO completion rate of 95%. A significant higher proportion of uncompleted questionnaires were completed after the patients had received the electronic reminder and after real-time monitoring. Conclusions Electronic reminders and real-time monitoring contributed to a very high completion rate in the study. To increase the quality of PRO data, we propose integrating these strategies in PRO studies, however highlighting that an increase in staff resources is required for implementation.

Background : The UK Myeloma Research Alliance recently introduced a new clinical prediction model for outcome in newly diagnosed multiple myeloma (MM) patients not eligible for autologous hematopoietic stem-cell transplantation (ASCT) (Lancet Haematology 2019; 6: e154-66). The score or Myeloma Risk Profile, MRP, includes WHO performance status (PS), the International Staging System (ISS), age, and C-reactive protein (CRP) as prognostic variables. First a score is calculated by the formula: Score = (PS - 2) * 0.199 + (age - 74.4) * 0.0165 + (ISS - 2) * 0.212 + (log(CRP + 1) - 2.08) * 0.0315, where PS and ISS are defined as numbers between 0-4 and 1-3, respectively, and CRP is in mg/L. Next, three risk groups are defined as 1) low risk: score < -0.256, 2) medium risk: -0.256 ≤ score ≤ -0.0283, or 3) high risk: score > -0.0283. The MRP score was generated based on two prospective clinical trial cohorts, the NRCI-Myeloma XI study (ISRCTN49407852) as training set or internal validation, and the NRCI-Myeloma IX study (Blood 2011; 118, 1231-38) as test set or external validation. Both trials investigated conventional oral alkylating agents, cyclophosphamide or melphalan, in combination with thalidomide, lenalidomide, and/or bortezomib; thus including drugs typically used in treatment of elderly MM patients. Establishment of the model included 1852 patients in the training set, and 520 patients in the test set. All patients were recruited as part of clinical trials and therefore fulfilled defined inclusion and exclusion criteria. To validate the MRP score in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients in the Danish National MM Registry. Methods : The Danish MM registry started 01 January 2005. It includes registration of all diagnosed MM patients in Denmark and given first- and second-line treatment. A data validation study has been performed (J Clin Epidemiology, 2016; 8: 583-587). At 31 December 2014, 2,926 newly diagnosed treatment demanding MM patients were registered, hereof 1,803 patients were above 65 years and found ineligible for ASCT, and constituted the patient population for this study. Results: Of 1,803 transplant in-eligible but treatment demanding newly diagnosed MM patients above 65 years 426 patients had one or more missing values for calculation of the MRP score, most often this was caused by missing ISS. Thus, 1,377 patients were evaluable with a median follow-up of 40.9 months. Patients were treated according to standard of care in Denmark during the 10-years registration period which included upfront conventional alkylating agent, mostly melphalan in 37.7%, thalidomide-based in 25.6%, bortezomib-based in 26.1%, lenalidomide based in 2.7%, and only palliative, mostly steroid-based in 7.9%. The distribution of the risk groups according to MRP was as follows: low risk 28.5%, medium-risk 25.1%, and high-risk 46.4%. Ccompared to the UK datasets we had a higher proportion of high-risk patients which undoubtedly reflects that our cohort is population based. Median survivals for the 3 risk groups are presented in Table 1 and overall survival curves illustrated in Figure 1. The model performed well in separating the patients into subgroups with different survival risks. In conclusion, our real life population-based data confirm that the MRP score is a robust and valuable risk assessment tool for elderly newly diagnosed MM patients older than 65 and not eligible for ASCT. An important advantage of the MRP score is that it is calculated from simple parameters that should be part of everyday diagnostic work-up. Disclosures Vangsted: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Plesner:Takeda: Consultancy; Oncopeptides: Consultancy; Genmab: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Research Funding. Frederiksen:Novartis: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Alexion: Research Funding; Abbvie: Research Funding. Abildgaard:Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding.

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.

[Background]: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. [Methods]: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m²) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. [Findings]: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. [Interpretation]: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma, This study was sponsored by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005–2012 period were identified in the Danish National Multiple Myeloma Registry. For each myeloma patient, 10 members of the general population matched by age and sex were chosen from the national Civil Registration System. Data on comorbidity in the myeloma patients and the general population comparison cohort were collected by linkage to the Danish National Patient Registry (DNPR). Cox proportional hazards regression models were used to evaluate the prognostic significance of comorbidity. The study included 2190 cases of multiple myeloma and 21,900 population controls. The comorbidity was increased in multiple myeloma patients compared with population controls, odds ratio (OR) 1.4 (1.1–1.7). The registration of comorbidity was highly increased within the year preceding diagnosis of multiple myeloma (OR 3.0 [2.5–3.5]), which was attributable to an increased registration of various diseases, in particular, renal disease with OR 11.0 (8.1–14.9). The median follow‐up time from diagnosis of multiple myeloma for patients alive was 4.3 years (interquartile range 2.4–6.3). Patients with registered comorbidity had increased mortality compared with patients without comorbidity, hazard ratio 1.6 (1.5–1.8). Multiple myeloma patients have increased comorbidity compared with the background population, in particular during the year preceding the diagnosis of myeloma.

AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim is to support research. Patients are registered with their unique Danish personal identification number, and the combined use of DMMR, other Danish National registries, and the Danish National Cancer Biobank offers a unique platform for population-based translational research.STUDY POPULATION: All newly diagnosed patients with multiple myeloma (MM), smoldering MM, solitary plasmacytomas, and plasma cell leukemia in Denmark are registered annually; ~350 patients. Amyloid light-chain amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome), monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance with polyneuropathy have been registered since 2014.MAIN VARIABLES: The main registered variables at diagnosis are patient demographics, baseline disease characteristics, myeloma-defining events, clinical complications, prognostics, first- and second-line treatments, treatment responses, progression free, and overall survival.DESCRIPTIVE DATA: Up to June 2015, 2,907 newly diagnosed patients with MM, 485 patients with smoldering MM, 64 patients with plasma cell leukemia, and 191 patients with solitary plasmacytomas were registered. Registration completeness of new patients is ~100%. A data validation study performed in 2013-2014 by the Danish Myeloma Study Group showed >95% data correctness.CONCLUSION: The DMMR is a population-based data validated database eligible for clinical, epidemiological, and translational research.

Several risk scores for disease progression in Smoldering Multiple Myeloma (SMM) patients 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 newly diagnosed SMM patients 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 ≥ 30g/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 the 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 ≥ 30g/l, we created a scoring system to identify low, intermediate and high risk SMM. This first population-based study of SMM patients confirms that an M-protein ≥ 30g/l and immunoparesis remain important risk factors for progression to MM. This article is protected by copyright. All rights reserved.

Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 × 109/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.

Graduate School of Health Sciences, Kumamoto University; Department of Morphological and Physiological Sciences, Kumamoto University; Faculty of Life Sciences, Department of Neurology, Kumamoto University; Diagnostic Unit for Amyloidosis, Kumamoto University Hospital; Faculty of Life Sciences, Department of Hematology, Kumamoto University; Department of Surgical Pathology, Kumamoto General Hospital; Division of Informative Clinical Sciences, Kumamoto University Introduction: AL amyloidosis is a disease featuring deposition of Ig light chain (LC). Diagnosis is determined if the presence of LC in amyloid deposits is detected with anti-LC chain antibodies. Poor prognosis cases, like detected amyloid deposits in heart, require the prompt diagnoses. However, in several cases, the existence of LC is not detected within amyloid deposits with immunohistochemistry (IHC) using conventional anti-LC antibodies although monoclonal lambda light chain in serum or urine was proved. In such cases, we found deposition of particular light chain constant region (immunoglobulin light chain constant region 2: IGLC2) at amyloid tissues. Materials and Methods: Amyloid tissues were either stained with conventional anti-human lambda LC rabbit antiserum (DAKO PO-0130) or rabbit anti-IGLC2 antibodies (made by SIGMA ALDLICH). Deposited peptide within amyloid lesion was examined using Congo Red staining followed by combination of laser micro-dissection and mass-spectrometry combining (LC-MS/MS). Plasma cells were purified with CD138-immunomagnetic beads from bone marrow aspirated obtained from two cases. Recombination of LC DNA in purified plasma cells was analyzed using PCR and direct nucleic acid sequencing. Results and Discussion: LC-MS/MS analysis revealed the presence of IGLC2 in all cases without showing positive signal by conventional antibody. Recombination of IGLC2 was detected in plasma cells. Deposition of IGLC2 was confirmed by IHC using anti-IGLC2 antibodies. The present data imply that “IGLC2-related amyloidosis” might be overlooked by conventional IHC unless utilizing mass-spectrometry. Utilization of antibodies for IGLC2 should contribute to improve quality of diagnosis for AL-amyloidosis. We consider that investigation of IGLC2 is important for not only making diagnosis but also analyzing pathogenesis of AL-amyloidosis.

BACKGROUND Research in palliative care is considered difficult due to the poor health of patients. However, patient-provided data are essential for a thorough description of patient symptomatology and for the evaluation of care. METHODS The authors examined the feasibility of a questionnaire-based study using the European Organization for Research and Treatment of Cancer quality-of-life instrument EORTC QLQ-C30, the Edmonton Symptom Assessment System (ESAS), and the Hospital Anxiety and Depression Scale (HADS) in cancer patients who were receiving palliative care. This report describes the symptomatology of participating patients and examines differences in symptomatology between patients in three palliative care functions: inpatient, outpatient, and palliative home care. RESULTS Of 267 eligible patients who were referred to a department of palliative medicine, initial self-assessment questionnaires were obtained from 176 patients (65.9%). The 91 nonparticipants were older and had lower Karnofsky Performance status (KPS) values than the participants. Almost all participating patients suffered from impaired role function and physical function and had high levels of pain, fatigue, and other symptoms. According to the HADS, 47% of patients suffered from depression. Outpatients had better scores than inpatients and patients in palliative home care for physical function, role function, cognitive function, depression, and inactivity. CONCLUSIONS It is possible to carry out a questionnaire-based study of symptomatology in consecutive cancer patients in palliative care, achieving rather complete data from the participants. The symptomatology in these patients was very pronounced. The questionnaires were able to detect clinically important differences between places of service. Cancer 2002;94:512–20. © 2002 American Cancer Society.