Brentuximab vedotin in combination with extended field radiotherapy as salvage treatment for primary refractory Hodgkin lymphoma To the Editor:Hodgkin lymphoma (HL) is a B-cell derived lymphoid malignancy that accounts for about 10% of all lymphomas. Despite most of patients being cured by modern regimens of chemotherapy and radiotherapy (RT), nearly 20% show primary refractoriness or relapse after initial remission. In these cases second-line chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation leads in nearly 50% of patients to a long lasting remission.For patients with HL relapsed/refractory (R/R) to more than two lines of therapy, there is no standard approach and prognosis is generally dismal. Therapeutic options include palliative chemotherapy, radiotherapy, and transplant procedures. More recently, Brentuximab Vedotin (BV), an anti-CD30 monoclonal antibody conjugated with Auristatin, showed therapeutic activity in 75% of patients with HL R/R to ASCT, with 35% complete response (CR) and median progression-free survival (PFS) of nearly 6 months [1]. Limited data are available regarding the combination of BV with chemotherapeutic agents while, the combination of BV with RT has not been reported so far.A 45-year-old male, with no significant comorbidities, was referred at our Centre on August 2013 for onset of multiple lympho-adenopaties (size varying from 2 to 7 cm and involving bilateral the cervical area and the right axillary) associated with fever, night sweats, fatigue, mild cough, and mild skin itching. Total white blood cell count was 39 3 10 9 /L (90% neutrophils, 4% lymphocytes), while hemoglobin and platelet count were 98 g/L and 635 3 10 9 /L, respectively; erythrocyte sedimentation rate was 91 mm/hr. After lateral cervical lymphonode biopsy and standard staging, the patient was diagnosed to have a sclero-nodular, classic HL, stage IIIs (spleen) B. The patient was started on standard ABVD chemotherapy program (Dacarbazine, Bleomycin, Vinblastine, and Doxorubicin) with rapid resolution of systemic symptoms and lymphonodes disappearance. A CT-PET evaluation after two cycles showed a picture of response with FDG uptake lower than liver (Deauville Score 3).After the fourth planned ABVD course, the patient had evidence of supradiaphragmatic progression with recurrence of right supraclavicular, axilla, and mediastinal involvement. A lymphonode biopsy confirmed the initial diagnosis of scleronodular classic HL. The patient was

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.

AimThe 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 populationAll 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 variablesThe 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 dataUp 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.ConclusionThe DMMR is a population-based data validated database eligible for clinical, epidemiological, and translational research.

Multiple myeloma (MM) is a malignant disorder characterized by the accumulation of neoplastic plasma cells in the bone marrow. Most patients suffer from osteolytic lesions that cause pain and reduced quality of life, and may result in hypercalcemia, fractures, and spinal root or spinal cord compression. At diagnosis 80% of patients already have pathological bone findings when evaluated with conventional radiography (1).MM causes increased bone resorption through osteoclast activation (2-6), and bone resorption is increased even in patients without osteolytic lesions (7). In addition, MM also causes decreased bone formation (8-11). AbstractObjectives: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions: Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. The trial was registered at clinicaltrial.gov with registration number NCT00436059.

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.