
Valentin Cabañas-PerianesHOSPITAL CLINICO UNIVERSITARIO VIRGEN DE LA ARRIXACA · HEMATOLOGY
Valentin Cabañas-Perianes
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Introduction
Publications
Publications (111)
Multiple myeloma (MM) remains incurable, with poor outcomes in heavily pre-treated patients with plasmacytomas. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option; however, outcomes after such therapy in patients with soft-tissue plasmacytomas and other bone lesions remain poorly understood. Data regarding th...
Introduction: In elderly patients (pts) with multiple myeloma (MM), MRD evaluation by NGF has shown to surpass conventional responses to predict patient outcomes with even a higher clinical impact as compared to younger transplant eligible cases. However, integrating MRD into routine clinical practice in these pts can be particularly challenging du...
Introduction: In 2006 the Spanish Group (PETHEMA/GEM) conducted a randomized trial (GEM05menos65, NCT00461747) for transplant eligible patients with newly diagnosed multiple myeloma showing a significant improvement in progression free survival with induction with VTD compared to TD and combination chemotherapy plus bortezomib (VBMCP/VBAD/B) (Blood...
Background: In patients with newly diagnosed multiple myeloma (NDMM) who are not candidates for transplant, VMP (bortezomib, melphalan, prednisone) and Rd (lenalidomide, dexamethasone) have been standard treatments. The Spanish Myeloma Group combined 9 cycles of VMP and 9 cycles of Rd, yielding good results for “fit” patients aged 65-80. They achie...
Introduction:
In multiple myeloma (MM), “Complete Response” (CR) is defined by the IMWG as negative immunofixation (IFE) on the serum and urine, disappearance of any soft tissue plasmacytomas, and less than 5% plasma cells (PC) in the bone marrow (BM). However, 24-hour urine collections and BM examinations can be challenging and uncomfortable for p...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...
Quantitative immuneprecipitation mass-spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared...
Chimeric antigen receptor (CAR) T‐cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M‐protein. Quantitative immunoprecipitation mass spectrometry (QIP‐MS) can accurately measure serum M‐protein with high sensitivity, and identify interferences c...
7544
Background: The activity and safety ofARI0002h, an academic autologous CAR T-cell product with a humanized single chain variable fragment targeting BCMA has been reported in a pilot multicenter clinical trial (CARTBCMA-HCB-01) treating 30 patients (pts) with RRMM (NCT04309981) (Oliver-Caldés, Lancet Onc 2023). Here, we describe results of the...
Purpose
B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overco...
BACKGROUND
CTCs and MRD are two small clones associated with a high risk of progression in smoldering MM (SMM) and post treatment relapse in active MM. Despite growing knowledge about their clinical significance and biological features, these questions remain unanswered: 1) What is the prognostic value of CTC and MRD kinetics? 2) Is MM disseminatio...
Background: There is evidence suggesting that CTCs are responsible for the spreading of clonal plasma cells (PC) inside and outside the bone marrow (BM). However, some pts unexpectedly have no CTCs at diagnosis. Here, we hypothesize that the absence of CTC defines a specific MM subtype with unique biological and clinical features. To our knowledge,...
Introduction: In patients (pts) with multiple myeloma (MM), analysis of minimal residual disease (MRD) dynamics in bone marrow by Next Generation Flow Cytometry (NGF) has shown that conversion of minimal residual disease (MRD) status modulates the risk of progression. Mass spectrometry measuring low-level monoclonal immunoglobulins has shown potent...
Background: CAR-T cells have revolutionized cancer immunotherapy, representing a promising option for R/R Multiple Myeloma (MM). Despite high remission rates observed after BCMA CAR-T therapy, many patients still relapse and knowledge of the molecular mechanisms governing CAR-T cell function is very limited. To shed some light on specific transcrip...
Background: We reported the safety and activity ofARI0002h, an academic autologous 4-1BB-based CAR T-cell product with a humanized scFv targeting BCMA in a pilot multicenter clinical trial (CARTBCMA-HCB-01) in 30 patients (pts) with relapsed/refractory multiple myeloma (RRMM) (NCT04309981) (Oliver-Caldés, Lancet Onc 2023). Here, we report results o...
Background: In transplant-ineligible patients (pts) with NDMM, VMP and Rd have been standards of care. The Spanish Myeloma Group examined induction with VMP followed by Rd, and results were particularly striking for “fit” pts aged 65-80 with a CR rate of 47% and an MRD negative rate (MRD(-)) of 20%. The median PFS was 34 months (m) and 4-years (yrs...
Background: CAR-T therapies targeting BCMA are a promising option for Multiple Myeloma (MM) patients. However, a significant number of patients still relapse and the limited persistence of CAR-T cells after infusion has been associated with lack of long-term responses. To shed light on the potential mechanisms driving CAR-T cell persistence we perf...
Background: The incidence of SPM in transplant eligible MM patients (pts) receiving lenalidomide maintenance is ≥ 12% and is associated with inferior overall survival (OS). Recent evidence suggests that while clonal hematopoiesis does not increase the risk of SPM, specific TP53 mutant HPC may expand under lenalidomide treatment and give rise to the...
From November 2014 to May 2017, 332 patients homogeneously treated with VRD induction, ASCT and VRD consolidation were randomized to receive maintenance therapy with RD (161 patients) vs IRD (171 patients). RD consisted of lenalidomide 15 mg/d from days 1-21 plus dexamethasone 20 mg/d on days 1-4 and 9-12 at 4-weeks intervals while in the IRD arm o...
Background:
Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients w...
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:...
Purpose:
Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under and over-treatment. We hypothesized that replacing bone marrow (BM) plasma cells (PCs) for circulating tumor cells (CTCs), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progressi...
Introduction
Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]).
Materials and methods
We developed a mathematical model to assess the prognostic value of serum MC response kinet...
Monitoring of the monoclonal protein (M-protein) by electrophoresis and/or immunofixation (IFE) has long been used to assess treatment response in multiple myeloma (MM). However, with the use of highly effective therapies, the M-protein becomes frequently undetectable and more sensitive methods had to be explored. We applied IFE and mass spectromet...
Background: ARI0002h is an academic lentiviral autologous second-generation CAR T-cell product with a 4-1BB co-stimulatory domain and a humanized single chain variable fragment targeting BCMA. In pre-clinical studies, ARI0002h has demonstrated potent in vitro and in vivo activity. Here, we report the first safety and efficacy results of the CARTBCM...
Background: Within the spectrum of monoclonal gammopathies, there are various subgroups with unique biological and clinical profiles. Namely, the presence of multiple myeloma (MM) and light-chain amyloidosis (AL) pts with MGUS-like phenotype has been hypothesized, but the criteria to identify this subgroup are poorly defined and lack clinical valid...
B ackground: ARI0002h is an academic autologous CAR T-cell product with a 4-1BB co-stimulatory domain and a humanized single chain variable fragment targeting BCMA, which is being tested in the CARTBCMA-HCB-01 clinical trial for patients (pts) with RRMM (NCT04309981). A fractionated infusion of 3x10 6 CAR+ cells (ARI0002h)/kg (10/30/60%) was admini...
Background
The 2/20/20 model to predict risk of transformation in SMM is established at diagnosis and not periodically re-evaluated, mainly because plasma cell (PC) quantification requires invasive bone marrow (BM) aspirates. It could be hypothesized that dynamic monitoring of tumor biomarkers could improve risk-stratification of SMM patients, but...
Background
Renal impairment (RI) is a common complication of multiple myeloma (MM) and has been associated with poor survival. MIR50 is an observational, prospective, multicenter study aimed to evaluate the renal response (RR) to treatment in patients (pts) with RRMM.
Methods
Renal and MM responses are evaluated according to IMWG criteria in pts w...
Improved therapies in multiple myeloma (MM) have forced a constant risk stratification update, first Durie-Salmon, then international scoring systems (ISS), next revised-ISS (RISS) including high-risk cytogenetic abnormalities (HRCAs) such as del(17p) and t(4;14), and now R2-ISS including 1q21 gain has been proposed. Predictive value of 1q21 gain b...
Key Points
Depth of standard response criteria after treatment intensification has limited prognostic value in transplant-eligible MM patients Persistence of MRD before maintenance eliminates survival differences across transplant-eligible MM patients in sCR, CR, VGPR and even PR
Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, but there are no studies investigating the differentiation stage of tumo...
Standard risk stratification (sRisk) guides clinical management in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM). Nonetheless, clinical results are considerably heterogeneous among patients with similar risk status. Blood and bone marrow samples from 276 MGUS, 56 SMM and 242 M...
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myel...
Introduction
Treatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory se...
Background: Transplant-eligible MM patients are achieving unprecedented CR rates with frontline therapy. This urges the question about what other tests are informative upon a negative immunofixation (IFx-), as well as if patients with short duration CR continue having dismal survival with modern frontline plus salvage therapies and if so, how to pr...
Background: Although great strides were made in the management of MM, our best chances to eradicate this malignancy may lie in preventing its progression.Most current models to predict risk of transformation in SMM are commonly established at diagnosis and not reevaluated over time, because some parameters such as tumor burden or genetic abnormalit...
Resumen
La anemia es un hallazgo frecuente en personas de edad avanzada que suele asociarse a una morbimortalidad no despreciable. Utilizando la definición de anemia propuesta por la OMS, más del 10% de las personas mayores de 65 años presentan síndrome anémico. Su etiología en edades avanzadas es compleja, abarcando un abanico que va desde los sín...
Resumen
El mieloma múltiple es una proliferación clonal de células plasmáticas en la médula ósea que se caracteriza por sintetizar una paraproteína detectable en el suero y/u orina, en la mayoría de las ocasiones, junto con daño orgánico evidenciable o biomarcadores de malignidad. Los síntomas típicos son los dolores óseos, principalmente, junto co...
Resumen
La información genética y molecular resulta crucial para el correcto diagnóstico y seguimiento de las patologías hematológicas malignas. También es necesario, en muchos casos, para un correcto diseño terapéutico, tanto porque ayuda a definir el pronóstico de los pacientes como porque ofrece dianas terapéuticas que se pueden utilizar con los...
Background and aims:
Bone disease extension in symptomatic multiple myeloma (MM) has prognostic implications. However, methods better than the traditional ones are necessary to establish the diagnosis according to the updated International Myeloma Working Group criteria (IMWG).
Magnetic resonance imaging (MRI) is a novel technique to detect bone le...
The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the...
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by intravascular hemolysis, cytopenias, and recurrent thrombosis. Thrombotic events are just the main cause of morbidity and mortality. Therefore, it is essential to detect them early to treat them and avoid sequels.
Aims
To analyze the diagnostic val...
Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adult...
Response criteria for multiple myeloma (MM) require monoclonal protein (M-protein)-negative status on both serum immunofixation electrophoresis (sIFE) and urine (uIFE) immunofixation electrophoresis for classification of complete response (CR). However, uIFE is not always performed for sIFE-negative patients. We analyzed M-protein evaluations from...
Introduction
High-throughput sequencing studies have rendered seminal knowledge in monoclonal gammopathies such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Unfortunately, the low incidence of AL amyloidosis and its typically low tumor burden, often masked by a polyclonal plasma cell (PC) background, account for the limited in...
Background: Since survival in AL mainly depends on the extent of organ involvement of patients at presentation, early diagnosis and risk stratification are key to improve patients' outcome. Therefore, together with surrogates of organ involvement, biomarkers identifying patients with MGUS or MM at greater risk of developing AL would be highly valua...
Background: MM and AL are the two most common malignant monoclonal gammopathies. Both diseases result from the accumulation of clonal PCs, but their clinical behavior is significantly different suggesting fundamental differences in disease biology. Previous attempts to identify genetic hallmarks that could explain such differences have been unsucce...
Background:
The regenerative and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) have raised great hope for their use in cell therapy. However, when intravenously infused, hMSCs fail to reach sites of tissue injury. Fucose addition in α(1,3)-linkage to terminal sialyllactosamines on CD44 creates the molecule known as hematop...
Background
Osteoporosis (OP) is a systemic bone disease characterised by decreased bone mass and deterioration of bone microarchitecture with increased brittleness and fracture risk. It associates high morbidity and mortality for patients and has a high impact on health expenditure. Bone marrow stromal mesenchymal stem cells (BM-MSC) give rise to o...
Aim:
To evaluate the clinical profile and effectiveness/safety of patients taking rivaroxaban in clinical practice.
Methods:
Retrospective study that included patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke between January 2012 and December 2016 in a tertiary hospital in Spain.
Results:
A tot...
Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ∼13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery...
Objective:
To assess the toxicity of a standardized triple intrathecal chemotherapy in onco-hematological adult patients and to establish risk factors of toxicity.
Method:
Observational and prospective study of standardized triple intrathecal chemotherapy administrations in onco-hematologic adult patients for 18 months.
Results:
There were some a...
Background aims
Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretatio...
Resumen
Introducción y objetivos
Los pacientes con síndrome de QT largo (SQTL) tienen una adaptación anormal del QT a los cambios bruscos de la frecuencia cardiaca producidos con la bipedestación. Este trabajo estudia la utilidad del test de bipedestación en una cohorte de pacientes con SQTL y evalúa si el fenómeno de «mala adaptación» del QT se n...
Background
Osteoporosis is a skeletal disease characterized by systemic bone loss with an increased risk to bone fractures, associated with high morbidity and mortality¹. Mesenchymal stem cells (MSC) from bone marrow (BM) are ideal candidates for the treatment of osteoporosis because they are able to differentiate to osteoblasts although its osteot...
Introduction and objectives:
Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy.
Methods:
E...
INTRODUCTION
Hemophilia A (HA) is a rare inherited genetic disorder linked to the X chromosome, characterized by joint bleeding in patients with severe disease with <1% of factor VIII (FVIII)(White et al. Thromb Haemost 2001). However, there are cases of severe HA with less bleeding than usual and it has been postulated that there must be other con...
Introduction: Dabigatran is a direct oral anticoagulant (DOAC) that has been proved effective and safe in preventing thromboembolic events experienced by patients with non-valvular atrial fibrillation (AF). This drug acts directly inhibiting thrombin and particularly affects the intrinsic and the final coagulation pathways. Thrombin is a platelet a...
Introduction:Renal impairment (RI) is a common complication of multiple myeloma (MM). Almost 20% of patients (pts) present with RI at diagnosis, while approximately 40%-50% of pts will develop RI during the course of their disease. However, there is little information on the renal response of pts with relapsed refractory MM (RRMM) receiving treatme...
Resumen
Introducción
Las anemias hemolíticas (AH), son un grupo heterogéneo de enfermedades que se caracterizan por destrucción precoz de los hematíes (hemólisis).
Patogenia. Manifestaciones clínicas
Las AH pueden ser congénitas o adquiridas. Las AH congénitas son consecuencia de alteraciones genéticas que determinan defectos en la membrana del h...
Resumen
Introducción
Las anemias hemolíticas (AH) engloban un grupo muy heterogéneo de anemias que tienen en común la destrucción precoz de los hematíes, proceso conocido como hemólisis. En consecuencia, existen ciertos datos de laboratorio comunes a todas ellas, como la anemia con aumento de reticulocitos, la elevación de la bilirrubina indirecta...
Resumen
Definición
La anemia es la disminución de la masa eritrocitaria por debajo de los valores necesarios para un transporte óptimo de oxígeno a los tejidos; los síntomas y signos específicos del síndrome anémico son consecuencia de este hecho y de las respuestas cardiovasculares compensadoras según la gravedad y la duración de la hipoxia.
Eti...
Resumen
Introducción
Los síndromes de insuficiencia medular son un grupo heterogéneo de trastornos clínica y fisiopatológicamente distintos, pero que se caracterizan por un fallo de función hematopoyética normal de la médula ósea.
Tipos
Pueden ser congénitos (anemia de Fanconi y anemia de Blackfand-Diamond) o adquiridos, y afectar de forma select...
Resumen
Introducción
Anemia es la disminución de la masa eritrocitaria por debajo de los valores necesarios para un transporte óptimo de oxígeno a los tejidos y los signos y síntomas derivados de la hipoxia tisular constituyen el síndrome anémico.
Valoración clínica inicial
El diagnóstico positivo de anemia se realiza al encontrar una disminución...
Introduction: In recent years, the multiple myeloma (MM) treatment (Tx) landscape has evolved considerably, with the approval of effective novel agents, such as immunomodulatory drugs (thalidomide, lenalidomide, and most recently, pomalidomide) and proteasome inhibitors (bortezomib and carfilzomib; Chng et al, Leukemia, 2014). However, most patient...
Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) lic...