Search results for "Multiple myeloma."

Corneal opacity and copper levels of the Lewis syndrome after systemic chemotherapy

2020

Abstract Purpose To report a female patient of biclonal Lewis syndrome which consists of a trias: biclonal gammopathy of undetermined significance, paraproteinemic keratopathy in form of a brownish discoid opacification at the level of Descemet's membrane and hypercupremia. After several years there was a conversion to multiple myeloma. Systemic chemotherapy led to a complete remission of multiple myeloma and to a normalization of the copper level in the blood that lasted five years. The corneal opacification remained unchanged. Observations A currently 66-year-old woman suffered from biclonal Lewis syndrome. On both eyes there is a central discoid yellow-brownish discoloration in the Pre-D…

Immunologic microenvironment and personalized treatment in multiple myeloma.

2013

Introduction: Multiple myeloma (MM) is characterized by generalized immune suppression and increased susceptibility to infections and secondary malignancies. Malignant plasma cells (PCs) modulate the bone marrow microenvironment to favor their own survival and proliferation. These events lead to a severe deregulation of immune effectors. Extensive studies have been conducted to unveil the mechanisms through which MM cells negatively modulate immunity and to develop therapeutical approaches for restoring an efficient anti-MM immune response. Areas covered: This review article covers both the immunosuppressive effects exerted by MM and the immunomodulatory potential of novel anti-MM agents. A…

Bortezomib Induces Anti–Multiple Myeloma Immune Response Mediated by cGAS/STING Pathway Activation

2021

Abstract The proteasome inhibitor bortezomib induces apoptosis in multiple myeloma cells and has transformed patient outcome. Using in vitro as well as in vivo immunodeficient and immunocompetent murine multiple myeloma models, we here show that bortezomib also triggers immunogenic cell death (ICD), characterized by exposure of calreticulin on dying multiple myeloma cells, phagocytosis of tumor cells by dendritic cells, and induction of multiple myeloma–specific immunity. We identify a bortezomib-triggered specific ICD gene signature associated with better outcome in two independent cohorts of patients with multiple myeloma. Importantly, bortezomib stimulates multiple myeloma cell immunogen…

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

2023

AbstractThe historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time …

Practical Considerations for the Daratumumab Management in Portuguese Routine Clinical Practice: Recommendations From an Expert Panel of Hematologists

2022

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients’ quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert pa…

Network meta-analysis of randomized trials in multiple myeloma: Efficacy and safety in frontline therapy for patients not eligible for transplant

2022

The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD) +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis (NMA) of 27 phase 2/3 randomized trials including a total of 12935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric use…

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide…

2022

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (…

ABSOLUTE LYMPHOCYTE COUNT AS PREDICTOR FOR SURVIVAL IN NEWLY DIAGNOSED ELDERLY PATIENTS WITH MULTIPLE MYELOMA

2011

Maxillary lesion presenting as a first sign of multiple myeloma : case report

2007

Plasma cell neoplasia is a lymphoid neoplastic proliferation of B cells. This denomination encloses multiple myeloma (MM), solitary bone plasmacytoma and extramedullary plasmacytoma. MM consists of a clonal proliferation of plasma cells based in the bone marrow, with various degrees of differentiation. Neoplastic cells usually produce great amounts of monoclonal light or heavy chains of immunoglobulin that can be detected in serum or urine. The disease is more frequently in men and the average age at diagnosis is about 60 years. The diagnosis is established by blood and urine exams and medullary biopsy. Patients may present renal failure, bone pain, fatigue, recurrent infections and nervous…

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

2022

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angioge…