156 research outputs found

    Wild-type transthyretin cardiac amyloidosis: When is a rare disease no longer a rare disease?

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    In this issue of JNC, Cuscaden and colleagues report the prevalence of cardiac uptake (a hallmark of cardiac amyloidosis) in patients undergoing routine {99m}^Tc-HMDP (hydroxymethylene diphosphonate) and {99m}^Tc-MDP (methylene diphosphonate) scintigraphy, suggesting a high prevalence of the disease increasing with age.

    Monoclonal gammopathy of undetermined significance and smoldering myeloma (SMM): a practical guide to management

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    Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are precursor conditions of symptomatic multiple myeloma (MM). Diagnostic principles are aimed at excluding MM requiring therapy, other conditions associated with paraproteins that may require different management, and risk stratifying patients for the purposes of tailored follow‐up and investigation. The International Myeloma Working Group have recently published a revised definition of MM, which singles out a small group of patients with smoldering multiple myeloma who are at very high risk of progression and organ damage; such patients are now included under the definition of MM and recommended to start anti‐myeloma treatment. Furthermore, the recently published National Institute of Health and Care Excellence guideline recommends cross‐sectional imaging techniques in place of skeletal survey. These recent recommendations are discussed, and practical guidance for investigation and management are presented

    A rare case of extensive biventricular cardiac sarcoidosis with reversible torrential tricuspid regurgitation

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    Reversal of torrential tricuspid regurgitation is rarely seen. We describe a case in which effective immunosuppression alongside conventional heart failure therapies lead to reversibility of torrential tricuspid regurgitation in a patient with cardiac sarcoidosis. We also discuss the diagnostic challenge in distinguishing cardiac sarcoidosis from other myocardial diseases in a patient presenting with biventricular failure

    A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis

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    In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib–dexamethasone vs 51% with physician’s choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32–0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib–dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options

    DT‐PACE/ESHAP chemotherapy regimens as salvage therapy for multiple myeloma prior to autologous stem cell transplantation

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    Routine use of novel agents to treat newly diagnosed and relapsed multiple myeloma (MM) produces high response rates and improved survival. However, 15–20% of patients have suboptimal responses and their management remains challenging.1 Traditional regimens, such as DT‐PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) and ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) are employed in patients with relapsed/refractory (RR) disease, and may bridge patients to autologous stem cell transplantation (ASCT).2-4 Originally developed to improve responses to traditional chemotherapy regimens, and enable stem cell mobilization,5-7 the role of infusional regimens in the context of novel agents is unclear, especially as recently reported series indicate relatively poor outcomes.8, 9 These regimens can be associated with significant toxicity,2 placing a burden on healthcare resources.10 We undertook a single‐centre retrospective analysis to assess the role of infusional regimens in RR MM patients to explore and identify features associated with clinical benefit. Relevant clinical information was obtained from electronic records. Overall response rate (ORR) and cytogenetic risk were assessed as per International Myeloma Working Group (IMWG) criteria (Table I).11 [Progression‐free (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox regression methods (time‐dependent where appropriate)]

    Defining Unmet Need Following Lenalidomide Refractoriness: Real-World Evidence of Outcomes in Patients With Multiple Myeloma

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    Background: The treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world. Methods: This was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment. Results: 198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was < 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group. Conclusion: These data demonstrate the poor outcomes of patients failing lenalidomidebased treatments in the real world, the highlight need for more effective treatments

    Search for AL amyloidosis risk factors using Mendelian randomization

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    In amyloid light chain (AL) amyloidosis, amyloid fibrils derived from immunoglobulin light chain are deposited in many organs, interfering with their function. The etiology of AL amyloidosis is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited by Mendelian randomization (MR) methodology to search for factors influencing AL amyloidosis risk. We performed a 2-sample MR analyzing 72 phenotypes, proxied by 3461 genetic variants, and summary genetic data from a GWAS of 1129 AL amyloidosis cases and 7589 controls. Associations with a Bonferroni-defined significance level were observed for genetically predicted increased monocyte counts (P = 3.8 × 10−4) and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 × 10−5). Two other associations with the TNFRSF (members 6 and 19L) reached a nominal significance level. The association between genetically predicted decreased fibrinogen levels may be related to roles of fibrinogen other than blood clotting. be related to its nonhemostatic role. It is plausible that a causal relationship with monocyte concentration could be explained by selection of a light chain–producing clone during progression of monoclonal gammopathy of unknown significance toward AL amyloidosis. Because TNFRSF proteins have key functions in lymphocyte biology, it is entirely plausible that they offer a potential link to AL amyloidosis pathophysiology. Our study provides insight into AL amyloidosis etiology, suggesting high circulating levels of monocytes and TNFRSF proteins as risk factors
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