The mechanism of action, pharmacological characteristics, and clinical utility of the amyloid depleter birtamimab for the potential treatment of AL amyloidosis.

Amyloid light chain (AL) amyloidosis is a progressive plasma cell disorder caused by amyloid deposition resulting in organ damage and failure. Current standard-of-care treatments target clonal plasma cells, the source of misfolded light chains (amyloid precursors), yet only half of patients with advanced disease survive ≥6 months. The amyloid depleter birtamimab is an investigational humanized monoclonal antibody that binds misfolded and light chains with high specificity and was designed to neutralize soluble toxic light chain aggregates and promote phagocytic clearance of deposited amyloid.

Development and Validation of Staging Systems for AA Amyloidosis.

Key Points: Patients with AA amyloidosis and age ≥65 years, eGFR <45 ml/min per 1.73 m, and -terminal type-B natriuretic peptide >1000 ng/L and/or type-B natriuretic peptide >130 ng/L at diagnosis have poorer survival. Proteinuria >3.

Healthcare Resource Utilization and Cost-of-Illness in Systemic Light Chain (AL) Amyloidosis in Europe: Results From the Real-World, Retrospective EMN23 Study.

Objectives: To report healthcare resource utilization (HCRU) and safety outcomes in systemic light chain (AL) amyloidosis from the EMN23 study.

Materials And Methods: The retrospective, observational, multinational EMN23 study included 4,480 patients initiating first-line treatment for AL amyloidosis in 2004-2018 and assessed, among other objectives, HCRU and safety outcomes. HCRU included hospitalizations, examinations, and dialysis; safety included serious adverse events (SAEs) and adverse events of special interest (AESIs).

Mining the amyloid-plaque proteome to uncover disease mechanisms in renal amyloidoses.

Beyond typing amyloid deposits and discovering new forms of amyloidosis, laser microdissection and mass spectrometry enable the analysis of the amyloid-plaque proteome constituents-amyloid fibrillar proteins, matrix and cellular components, and absorbed blood-borne proteins. Charalampous et al. analyzed the amyloid-plaque proteomes of the 7 most common renal amyloidoses to gain preliminary mechanistic insights on cellular and molecular perturbations elicited during gradual amyloid deposition and potential tissue repair or damage mechanisms.

World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM).

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms).

Role of autologous haematopoietic cell transplantation in the treatment of systemic light chain amyloidosis in the era of anti-CD38 monoclonal antibodies.

The primary goal of the initial treatment in systemic light chain amyloidosis is to obtain a rapid and profound haematological response as safely as possible, coupled with supportive care by a multidisciplinary team. The treatment landscape has evolved with the introduction of highly effective therapies targeting the plasma cell clones, which can attain high rates of haematological complete response with minimal treatment-related morbidity and mortality. Consequently, the role of high-dose melphalan followed by autologous haematopoietic cell transplantation (HDM-AHCT) is being analysed, particularly considering the absence of randomised controlled trial data supporting its superiority over standard-dose therapies in systemic light chain amyloidosis treatment.

Lenalidomide plus Dexamethasone Combination as First-Line Oral Therapy of Multiple Myeloma Patients: A Unicentric Real-Life Study.

Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.

The Cryo-EM STRUCTURE of Renal Amyloid Fibril Suggests Structurally Homogeneous Multiorgan Aggregation in AL Amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is caused by the aberrant production of amyloidogenic light chains (LC) that accumulate as amyloid deposits in vital organs. Distinct LC sequences in each patient yield distinct amyloid structures. However different tissue microenvironments may also cause identical protein precursors to adopt distinct amyloid structures.

Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group.

Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L is detected, then a renal biopsy is needed.

Amyloidogenic light chains impair plasma cell survival.

Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils in organs. The lack of suitable models has hindered the investigation of the disease mechanisms. Our aim was to establish AL LC-producing plasma cell lines and use them to investigate the biology of the amyloidogenic clone.

Magnetic resonance neurography and diffusion tensor imaging of the sciatic nerve in hereditary transthyretin amyloidosis polyneuropathy.

The therapeutic advance in hereditary transthyretin amyloidosis (ATTRv amyloidosis) requires quantitative biomarkers of nerve involvement in order to foster early diagnosis and monitor therapy response. We aimed at quantitatively assessing Magnetic Resonance Neurography (MRN) and Diffusion Tensor Imaging (DTI) properties of the sciatic nerve in subjects with ATTRv-amyloidosis-polyneuropathy (ATTRv-PN) and pre-symptomatic carriers (ATTRv-C). Twenty subjects with pathogenic variants of the TTR gene (mean age 62.

A Strategy for the Selection of RT-qPCR Reference Genes Based on Publicly Available Transcriptomic Datasets.

In the next-generation sequencing era, RT-qPCR is still widely employed to quantify levels of nucleic acids of interest due to its popularity, versatility, and limited costs. The measurement of transcriptional levels through RT-qPCR critically depends on reference genes used for normalization. Here, we devised a strategy to select appropriate reference genes for a specific clinical/experimental setting based on publicly available transcriptomic datasets and a pipeline for RT-qPCR assay design and validation.

Report of Consensus Panel 6 from the 11 th International Workshop on Waldenström's Macroglobulinemia on Management of Waldenström's Macroglobulinemia Related Amyloidosis.

Consensus Panel 6 (CP6) of the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the state of the art for diagnosis, prognosis, and therapy of AL amyloidosis associated with Waldenström macroglobulinemia (WM). Since significant advances have been made in the management of AL amyloidosis an update for this rare disease associated with WM was necessary. The key recommendations from IWWM-11 CP6 included: (1) The need to improve the diagnostic process by recognizing red flags and using biomarkers and imaging; (2) The essential tests for appropriate workup; (3) The diagnostic flowchart, including mandatory amyloid typing, that improves the differential diagnosis with transthyretin amyloidosis; (4) Criteria for therapy response assessment; (5) State of the art of the treatment including therapy of wild type transthyretin amyloidosis associated with WM.

Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study.

Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax.

Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies.

Purpose: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated.

Patients And Methods: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis.

Electrocardiographic features and rhythm disorders in cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or hereditary variants, or immunoglobulin light chains misfolding. It is characterized by an increased left ventricular (LV) mass and diastolic dysfunction, which can lead to heart failure with preserved ejection fraction and/or conduction disturbances. The diagnosis is based on invasive pathology demonstration of amyloid deposits, or non-invasive criteria using advanced cardiovascular imaging techniques.