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Publications (113)
Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) 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...
Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) p...
Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical re...
Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such...
Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myelo...
The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase 2 study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexa...
Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment...
Introduction. Immunoparesis (IP) or the suppression of uninvolved immunoglobulins (Ig) is a very common finding in multiple myeloma (MM) patients at diagnosis that confers worse prognosis. In addition to classic total Ig, IP can be measured by the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC). Previously, we have reported that...
BACKGROUND
MRD is an established test in MM clinical trials but not in routine practice. A hindrance to its wider adoption is invasive bone marrow (BM) aspirates. Thus, the possibility of assessing MRD using minimally invasive methods could be paramount to facilitate its transition from clinical trials to routine practice, but also to improve patie...
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...
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:
Most patients with multiple myeloma (MM) relapse or become refractory, resulting in high health care costs. However, real-world data regarding the utilization of health care services among the relapsed/refractory MM (RRMM) population are scarce.
Methods:
Observational, cross-sectional, multicenter study of the utilization of health c...
Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting...
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...
Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from...
Daratumumab monotherapy was first investigated in GEN501 and SIRIUS trials in relapsed/refractory multiple myeloma (RRMM) patients, showing positive results. However, there is a lack of information on plasmacytoma response. We described a real-world study of 43 RRMM patients who received daratumumab monotherapy. The overall response rate (ORR) was...
Background: Treatment of multiple myeloma (MM) has significantly evolved in the last decade leading to significant improvements in survival. Still, cure remains elusive and new combinations incorporating drugs with novel mechanism of action are needed to rescue patients becoming resistant to standard of care. Selinexor is an exportin-1 (XPO1) inhib...
Background: The Spanish Myeloma Group (GEM) demonstrated that post-transplant maintenance with thalidomide plus bortezomib was superior to thalidomide alone, although this combination was associated with a high rate of peripheral neuropathy. Lenalidomide is currently the standard postransplant maintenance treatment, and its association with ixazomi...
Introduction:
Treatment of relapsed and/or refractory multiple myeloma (RRMM) should be established based on multiple factors, including previous treatment and the sociodemographic/clinical characteristics of the patients. However, patients enrolled in randomized-controlled trials often do not mirror the scenario encountered in real-world practice...
Background
t(11;14) is the most frequently IgH rearrengement in newly diagnosed multiple myeloma (NDMM) with a 15-20% prevalence and is considered a standard-risk cytogenetic abnormality (SR). However, t(11;14) is controversial since recent reports describe inferior outcomes in contrast to other SR patients. We analyze the long-term outcome of t(11...
Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not...
Key Points
VRD was effective and well tolerated before ASCT; 33.4% complete response/28.8% minimal residual disease–negative after 6 induction cycles. Responses deepened with VRD throughout induction and over the course of treatment with few discontinuations due to toxicity.
Background
Multiple myeloma (MM) affects elderly individuals with two‐thirds of patients aged >65 years at diagnosis, 35% ≥75 and 10% ≥80. In general, routine clinical practice is based on the results of large, multicenter, randomized clinical trials. However, despite efforts from cooperative groups, patients enrolled in trials are generally younge...
Background and Purpose
Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM), despite lenalidomide based-triplets proven superiority. Recent trials revealed that up to 20% of patients obtained long-term benefit from Ld alone. The aim of this multi-c...
Following the publication of this article, the author notes that the following information was missed from the acknowledgments section:
Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyze...
Introduction: Disease control at five years would be a desirable endpoint for elderly multiple myeloma (MM) patients; however, the percentage of cases reaching this objective as well as the biomarkers to predict it, are not well defined.
Objective and design: In order to gain further insight about long-term disease control (>5 years progression-fre...
Background: The randomized PETHEMA/GEM phase III trial GEM05menos65 (www.clinicaltrials.gov NCT00461747) demonstrated that pretransplant induction therapy with VTD resulted in a significantly higher CR rate both, pretransplant and postransplant and in a significantly longer progression-free survival (PFS) when compared with thalidomide/dexamethason...
Although survival of elderly myeloma patients has significantly improved there is still a subset of patients who, despite being fit and achieving optimal responses, will die within 2 years of diagnosis due to myeloma progression. The objective of this study was to define a scoring prognostic index to identify this group of patients. We have evaluat...
We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC...
Overall survival (PFS) relationships to the absolute value of involved serum heavy-light chain (isHLC) and the ratio of highly abnormal sHLC (HA-sHLCr).
(Figure A in S2 Fig) OS among patients with absolute values of isHLC <30 g/L (blue, median OS: 67 mo), 30–50 g/L (green, median OS: 57 mo), or >50 g/L (red, median OS: 51 mo). (Figure B in S2 Fig)...
Demographics and baseline characteristics of patients (N = 819).
*3 cases were classified as oligosecretory myeloma.
(DOC)
Multivariable analysis of prognostic factors measured at diagnosis* (PFS).
OR, odds ratio; CI: confidence interval; LDH: lactate dehydrogenase; HA-sHLCr: highly abnormal serum heavy-light chain ratios; FISH: fluorescence in situ hybridization
* Variables initially included: Age, LDH, HA-sHLCr, High vs. low-risk FISH.
(DOC)
Relationships between treatment response categories and involved-sHLC levels (<5 or ≥5 g/L) and sHLC ratios (normal or abnormal).
CR: complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease
*An involved-sHLC <5 g/L was related to a better treatment response (Χ2, P<0.0001).
**Normalizati...
Overall survival (OS) relationships to serum free light chain (sFLC) evaluations.
(Figure A in S1 Fig) OS among patients with “highly abnormal” sFLC ratios (<0.03 or >32, red lines, median OS: 71.8 mo) compared to those with normal sFLC ratios (0.03–32, blue lines, median OS: 74.9 mo). (Figure B in S1 Fig) OS among patients with normal (blue, media...
New agent based first line induction treatments in newly diagnosed MM patients provide benefits beyond first progression free survival that contribute to a significant improvement in OS.
El Capítulo I aborda la distribución funcional de la renta, es decir, la distribución del PIB entre los factores productivos que han contribuido a su obtención. El interés de analizar la distribución de la renta desde una perspectiva funcional es su utilidad para comprender y analizar tanto la evolución de la masa salarial, principal determinante d...
Objective:
Clinical trials for multiple myeloma patients using novel agent-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS), however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potentia...
The phase III trial GEM05MENOS65 randomized 390 patients 65 years-old or younger with newly diagnosed symptomatic MM to receive induction with thalidomide/dexamethasone (TD), bortezomib/thalidomide/dexamethasone (VTD) and VBMCP/VBAD/bortezomib (VBMCP/VBAD/B) followed by ASCT with MEL-200. After ASCT a second randomisation was performed to compare t...
Este artículo cuantifica el nivel de pobreza multidimensional en España y
sus comunidades autónomas con los datos proporcionados por la Encuesta
de Condiciones de Vida de los años 2008 y 2011. Se utilizan diferentes medidas
de pobreza a partir de la metodología del recuento y se presenta una
propuesta para el establecimiento de líneas relativas de...
Background:Novel insights into the biology of myeloma cells have led to the identification of relevant prognosis factors.Cytogenetic abnormalities (CA) has become one of the most important prognostic factors, and the presence of t(4;14), t(14;16) or del(17p) are associated with poor prognosis. Although there are some reports indicating that 1q gain...
The notion that plasma cells (PCs) are terminally-differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferati...
Key Points
MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespective of age or cytogenetic risk. Second-generation MFC immune profiling concomitant to MRD monitoring also helped to identify patients with different outcomes.
Key Points
We report for the first time the biological features of MRD cells in MM and unravel that clonal selection is already present at the MRD stage. MRD cells show a singular phenotypic signature that may result from persisting clones with different genetic and gene expression profiles.
Este artículo cuantifica el nivel de pobreza multidimensional en España y
sus comunidades autónomas con los datos proporcionados por la Encuesta
de Condiciones de Vida de los años 2008 y 2011. Se utilizan diferentes medidas
de pobreza a partir de la metodología del recuento y se presenta una
propuesta para el establecimiento de líneas relativas de...
Introduction:
The sFLC assay was introduced in 2006 for diagnosis and monitoring of gammopathies, being currently the normalization of its ratio one of the requirements for defining stringent complete response (sCR). The new sHLC assay allows identifying the different light chain types bound to each heavy chain (i.e. separate the amount of IgG Κ fr...
Background: MM usually affects elderly patients and although novel agents-based combinations have substantially improved MM outcome, it is possible that this benefit would be particularly relevant for the "youngest-elderly" patients (65-80y). According to the frailty score published by IMWG, the chronological age ≥80 years identifies itself a frail...
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...
Background: Novel insights into the biology of myeloma cells have led to the identification of relevant prognosis factors. CA has become one of the most important prognostic factors, and the presence of t(4;14), t(14;16) or del(17p) are associated with poor prognosis. Although there are some reports indicating that 1q gains may be considered as a p...
Bortezomib plus melphalan and prednisone (VMP) and lenalidomide plus low-dose dexamethasone (Rd) are 2 standards of care for elderly untreated multiple myeloma (MM) patients. We planned to use VMP and Rd for 18 cycles in a sequential or alternating scheme. Patients (233) with untreated MM, >65 years, were randomized to receive 9 cycles of VMP follo...
Introduction:Renal impairment (RI) is a common complication in multiple myeloma (MM) with an incidence of 20-40%, due to the older age of the affected patients (pts) and the nature of the disease. Prognosis of pts with RI has improved in recent years (yrs), but remains closely associated with the recovery of renal function. There is little informat...
Background and Objectives: Recently, knowledge of the specific genetic markers responsible for cancer malignancies and their associated signaling pathways have generated many new targets that promise to increase drug efficacy while reducing side effects such as hematotoxicity. Although hematotoxicity is widely assumed to be the result of depleting...
Background: The randomized PETHEMA/GEM phase III trial GEM05menos65 (www.clinicaltrials.gov NCT00461747) demonstrated that pretransplant induction therapy with VTD resulted in a significantly higher CR rate both, pretransplant and postransplant and in a significantly longer progression-free survival (PFS) when compared with thalidomide/dexamethason...
Background: Autologous stem-cell transplantation (ASCT) is the standard of care for younger patients with multiple myeloma (MM). The degree of tumor reduction after ASCT is the crucial factor associated with a prolonged PFS and OS, being the M-protein decrease at the time of transplant the most important predictor of residual disease after ASCT. Wh...
B-cell lymphopoiesis ends in terminally differentiated bone marrow (BM) plasma cells (PCs). While initially PCs have been viewed mainly as short-lived end-stage B-cells, there is now evidence that this is a heterogeneous cellular compartment in which new-born plasmablasts and long-lived PCs also coexist. The transition between both is characterized...
Key Points
Melphalan, in combination with bortezomib, should be maintained as one of the standards of care for the treatment of elderly MM patients. Complete response and particularly flow complete response should be an important goal in the treatment of elderly myeloma patients.
MRD monitoring is emerging as a powerful prognostic biomarker in MM. In addition to its utility to redefine the depth of response achieved after therapy, the MRD clone represents, from a biological point of view, a very small fraction of tumor cells that are truly chemoresistant, potentially quiescent (not producing M-protein), and able to recapitu...
The effectiveness of rituximab maintenance therapy in the treatment of chronic lymphocytic leukemia has been investigated in a phase 2 clinical trial that included an initial treatment with rituximab 500 mg/m2 on day 1 (375 mg/m2 the first cycle), fludarabine 25 mg/m2 on days 1 to 3, cyclophosphamide 200 mg/m2 on days 1 to 3, and mitoxantrone 6 mg/...
The gene expression profiles (GEPs) of 96 selected genes were analysed by real-time quantitative polymerase chain reaction (qPCR) with a TaqMan low-density array card in isolated tumour plasma cells (PCs) from 157 newly diagnosed multiple myeloma (MM) patients. This qPCR-based GEP correctly classified cases following the Translocation-cyclin D clas...
Cytotoxic T lymphocyte antigen 4 (CTLA-4) plays a key inhibitory role during T lymphocyte activation. The CTLA4 gene is translated into two proteic isoforms: a full-length protein (flCTLA-4) and a soluble counterpart. We explored the expression of both isoforms on healthy subjects. Whereas in non-stimulated cells the flCTLA-4 isoform is predominant...
3930
Chemoimmunotherapy combination regimens achieve high rates of negative minimal residual disease responses in CLL, which has been correlated with prolonged PFS and OS. In the present study, we addressed the prognostic value of MRD levels obtained after rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) induction treatment in the...
334
Introduction
The Spanish Myeloma Group (PETHEMA/GEM) conducted a randomized phase III trial comparing induction with thalidomide/dexamethasone (TD) vs. bortezomib/thalidomide/dexamethasone (VTD) vs. VBMCP/VBAD/Bortezomib (VBMCP/VBAD/B) in patients 65 years-old or younger with newly diagnosed symptomatic MM and ASCT with MEL-200 followed by mai...
Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received...
The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endp...
477
In 2005, Spanish Myeloma Group (GEM/Pethema) activated a two-stage, randomized trial including 260 elderly untreated myeloma patients. In the first stage, patients received induction therapy based mainly on a once per week dosing of bortezomib in combination with prednisone plus either melphalan (VMP) or thalidomide (VTP). The results of this f...
3962
Introduction
In April 2006, the Spanish Myeloma Group (PETHEMA/GEM) activated a randomized phase III trial comparing induction with TD vs. VTD vs. VBMCP/VBAD/Bortezomib (VBMCP/VBAD/B) in patients 65 years-old or younger with newly diagnosed symptomatic MM and ASCT with MEL-200 followed by maintenance with thalidomide/bortezomib (TV) vs. thali...
1412
Over the last decade, numerous new drugs have been incorporated in the treatment armamentarium of multiple myeloma (MM). However, there is not much information on the role of single nucleotide polymorphisms (SNPs) regarding toxicity and efficacy of the new myeloma therapies. Aims: to analyze the influence of genetic polymorphisms on toxicity a...
293
The effectiveness of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) followed by rituximab maintenance in the treatment of CLL has been investigated in a phase II clinical trial that includes two treatment parts. First, patients were given induction therapy with R-FCM up to 6 cycles, achieving an overall response (OR) rate of...