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Purpose: Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D 3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D 3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D 3 supplementation on PN., Methods: Thirty-nine MM patients with inadequate (< 75 nmol/L [= 30 ng/mL]) 25-hydroxyvitamin D (25(OH)D) levels were included in this multicenter, prospective, single-arm study, of whom 35 patients completed the study. They received oral vitamin D 3 for 6 months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200 IU/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN., Results: Median 25(OH)D increased from 38 (IQR 32-52) nmol/L at baseline to 77 (IQR 72-87) nmol/L after 6 months (P < 0.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50-75 nmol/L. Furthermore, in 37% of the participants, PN severity decreased (P = 0.007)., Conclusion: The use of substantially higher vitamin D 3 doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research., (© 2023. The Author(s).)

Rationale: While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time., Objective: To determine the effect of different treatment periods (1996-2000, 2001-2006 and 2007-2011) on the risk of fractures in patients with multiple myeloma., Methods: This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use., Results: The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: OR adj [95% CI] 1996-2000: 1.7[1.3-2.3]; 2001-2006: 1.3[1.1-1.6]; 2007-2011: 1.7[1.4-2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: OR adj [95% CI] 1996-2000: 3.5[1.4-8.6]; 2001-2006: 4.0[1.9-8.2]; 2007-2011: 3.0[1.6-5.7])., Conclusions: Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions., Competing Interests: Declaration of competing interest BO, JD, MH, RK, NV, PV and ER declare that they have no conflicts of interest. JB reports grants and personal fees from Eli Lilly, grants and personal fees from Amgen, and personal fees from Sanofi, outside the submitted work. FV currently supervises a PhD student who is also employed with F. Hoffmann la Roche Ltd., Basel Switzerland. He has not received any reimbursements for this, and the student's research topics are not related to this publication., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients with multiple myeloma (MM) are known to be immune incompetent and experience higher incidences of infectious diseases. However, infective endocarditis (IE) is rarely observed in patients with MM and Morganella morganii (M. morganii) has rarely been associated with IE., Case Presentation: A 72-year-old female receiving 4th line treatment for MM presented with fever and concomitant confusion. Urinary culture revealed growth of Escherichia coli, wherefore broadspectrum penicillin and high-dose corticosteroids were initiated. However, blood cultures showed growth of M. morganii. Fluoroquinolone was added due to penicillin-resistance of the Morganella species. Two days after admission, the patient acutely deteriorated with hemodynamic instability. Gentamicin and high dose corticosteroids were added. Echocardiography showed marked aortic valve vegetation with severe aortic valve regurgitation, leading to the diagnosis of bacterial endocarditis of the native aortic valve. Shortly after diagnosis, the patient died. At autopsy, vegetation with gram-negative rods in the native aortic valve was observed, confirming the diagnosis of M. morganii-endocarditis. Additional staining for amyloid confirmed advanced light-chain (AL) amyloidosis with extensive amyloid depositions of the aortic valve and valvular damage as complications of her MM., Conclusions: Our case suggests that IE with M. morganii was facilitated by the combination of the cardiac amyloidosis with valvular impairment and the profound immune deficiency caused by the several chemo-immunomodulatory treatment lines and the MM itself. This case further illustrates that awareness for rare opportunistic infections in an era with growing potential of combined chemoimmunotherapy is warranted.

Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1.08, 95% CI = 0.67-1.74, p = .76). In multivariable analysis, baseline eGFR <30 ml/min (HR = 1.71), age >70 yrs (HR = 1.77), hypercalcemia (HR = 2.73), lambda Bence-Jones (HR= 1.76), and initial treatment regimen (HR = 0.89 for thalidomide, HR = 1.95 in treatment regimens without novel agents and HR = 3.60 for no chemotherapy, all vs. bortezomib) were associated with decreased OS. In conclusion, achieving renal response was not associated with improved OS.

Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma (MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors (HIF), vascular endothelial growth factor (VEGF, also termed VEGFA) and micro-vessel density (MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma (EMP) while 66% had a solitary plasmacytoma of the bone (SBP). Median follow-up was 89 months, (7-293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2α (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy., (© 2016 John Wiley & Sons Ltd.)

Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow-up was 27·1 (0·46-54·4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18·4 months (range 0·13-43·5) and the median OS was 28·1 months (range 0·13-54·4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate., (© 2015 John Wiley & Sons Ltd.)

Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma ( MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors ( HIF), vascular endothelial growth factor ( VEGF, also termed VEGFA) and micro-vessel density ( MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma ( EMP) while 66% had a solitary plasmacytoma of the bone ( SBP). Median follow-up was 89 months, (7-293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2α (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow- up was 27.1 (0.46-54.4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18.4 months (range 0.13-43.5) and the median OS was 28.1 months (range 0.13-54.4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate. [ABSTRACT FROM AUTHOR]