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1.
Front Immunol ; 12: 792609, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34880879

RESUMEN

Background: We previously reported algorithms based on clinical parameters and plasma cell characteristics to identify patients with smoldering multiple myeloma (SMM) with higher risk of progressing who could benefit from early treatment. In this work, we analyzed differences in the immune bone marrow (BM) microenvironment in SMM to better understand the role of immune surveillance in disease progression and to identify immune biomarkers associated to higher risk of progression. Methods: Gene expression analysis of BM cells from 28 patients with SMM, 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and 22 patients with symptomatic MM was performed by using Nanostring Technology. Results: BM cells in SMM compared to both MGUS and symptomatic MM showed upregulation of genes encoding for key molecules in cytotoxicity. However, some of these cytotoxic molecules positively correlated with inhibitory immune checkpoints, which may impair the effector function of BM cytotoxic cells. Analysis of 28 patients with SMM revealed 4 distinct clusters based on immune composition and activation markers. Patients in cluster 2 showed a significant increase in expression of cytotoxic molecules but also inhibitory immune checkpoints compared to cluster 3, suggesting the presence of cytotoxic cells with an exhausted phenotype. Accordingly, patients in cluster 3 had a significantly longer progression free survival. Finally, individual gene expression analysis showed that higher expression of TNF superfamily members (TNF, TNFAIP3, TNFRSF14) was associated with shorter progression free survival. Conclusions: Our results suggest that exhausted cytotoxic cells are associated to high-risk patients with SMM. Biomarkers overexpressed in patients with this immune gene profile in combination with clinical parameters and PC characterization may be useful to identify SMM patients with higher risk of progression.


Asunto(s)
Médula Ósea/fisiología , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , Mieloma Múltiple/inmunología , Mieloma Múltiple Quiescente/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinogénesis , Microambiente Celular , Estudios de Cohortes , Citotoxicidad Inmunológica/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de Punto de Control Inmunitario/genética , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Fenotipo , Mieloma Múltiple Quiescente/genética , Mieloma Múltiple Quiescente/mortalidad , Análisis de Supervivencia , Factor de Necrosis Tumoral alfa/genética
2.
Blood Cancer J ; 11(11): 186, 2021 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-34836942

RESUMEN

The Mayo-2018 smoldering multiple myeloma (SMM) risk score is used routinely in the clinical setting but has only been validated at diagnosis. In SMM patients, the progression risk decreases over time. However, the utility of applying risk stratification models after diagnosis is unknown. We retrospectively studied 704 SMM patients and applied the Mayo 2018 and IMWG-2020 risk stratification models at annual landmark timepoints up to 5 years post diagnosis. The Mayo-2018 and IMWG-2020 models reliably stratified patients based on progression risk when applied post diagnosis. The respective 2-year progression risk in Mayo-2018 high risk patients versus IMWG-2020 intermediate-high risk patients was 51% versus 62% at the 1-year landmark and 47% versus 45% at the 4-year landmark. We showed that patients categorized at Mayo-2018 high-risk at follow-up had a similar risk of progression if the baseline risk assessment was low-intermediate versus high-risk (HR 1.04, 95% CI 0.46-2.36, p = 0.931 at 5-year landmark). Patients migrating to a higher risk category during follow up had a higher progression risk compared to patients with stable/decreased risk categorization. Our findings support the use of these risk scores post-diagnosis and suggest that patients evolving to a high-risk category may benefit from early intervention therapeutic approaches.


Asunto(s)
Mieloma Múltiple Quiescente/mortalidad , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Mieloma Múltiple Quiescente/diagnóstico , Mieloma Múltiple Quiescente/terapia , Tasa de Supervivencia
3.
Blood Cancer J ; 11(6): 120, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-34168119

RESUMEN

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07-5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45-2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.


Asunto(s)
Antígeno de Maduración de Linfocitos B/sangre , Gammopatía Monoclonal de Relevancia Indeterminada , Proteínas de Neoplasias/sangre , Mieloma Múltiple Quiescente , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Valor Predictivo de las Pruebas , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/mortalidad , Tasa de Supervivencia
4.
Eur J Haematol ; 107(3): 318-323, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33993536

RESUMEN

Multiple myeloma (MM) patients with smoldering (S) disease are defined by a lack of CRAB/SLiM criteria but may transform into disease requiring treatment. The International Myeloma Working Group risk stratification model for SMM uses serum M-protein, serum-free light chain ratio, and bone marrow plasma cell percentage. We investigated whether baseline serum B-cell maturation antigen (sBCMA) levels are predictive of disease progression among 65 patients with SMM. A receiver operating characteristic curve was used to establish a definition for high-risk baseline sBCMA. Mantel Byar analysis was used to examine whether high-risk sBCMA was correlated with shorter time to transformation, and a time-dependent cox proportional hazard was used to determine whether it is independent of other risk factors. A z test for proportions was used to compare the percentage of patients that progressed among high-risk versus low-risk sBCMA patients. A baseline sBCMA level ≥137.5 mg/ml was found to be the optimal cutoff between high- and low-risk SMM patients. Patients with high-risk sBCMA levels had a shorter time to transformation (P = .000332). sBCMA was also higher at the time of transformation than baseline levels (P = .0116). sBCMA was the only variable found to be significantly predictive of time to transformation and additionally was found to be independent of other risk factors. In this study, we have shown for the first time that sBCMA levels predict transformation of SMM to active disease and that these levels increase at the time of transformation. These results are consistent with other studies showing that active MM patients undergoing therapy with higher baseline sBCMA levels are more likely to progress early and its levels increase at the time of disease progression.


Asunto(s)
Antígeno de Maduración de Linfocitos B/sangre , Biomarcadores de Tumor/sangre , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno de Maduración de Linfocitos B/inmunología , Biomarcadores de Tumor/inmunología , Progresión de la Enfermedad , Femenino , Glicoproteínas/sangre , Glicoproteínas/inmunología , Humanos , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Factores de Riesgo , Mieloma Múltiple Quiescente/inmunología , Mieloma Múltiple Quiescente/mortalidad
5.
Ann Hematol ; 100(2): 437-443, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33392702

RESUMEN

We analyzed variations in terms of chromosomal abnormalities (CA) by fluorescence in situ hybridization (FISH) analysis on purified bone marrow plasma cells throughout the progression from monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (MGUS/SMM) to newly diagnosed MM/plasma cell leukemia (NDMM/PCL) at diagnosis and from diagnostic samples to progressive disease. High risk was defined by the presence of at least del(17p), t(4;14), and/or t(14;16). 1p/1q detection (in the standard FISH panel from 2012 onward) was not available for all patients. We analyzed 139 MM/PCL diagnostic samples from 144 patients, with a median follow-up of 71 months: high-risk CA at diagnosis (MGUS/SMM or NDMM) was present in 28% of samples, whereas 37-39% showed high-risk CA at relapse. In 115 patients with NDMM who evolved to relapsed/refractory MM, we identified 3 different populations: (1) 31/115 patients (27%) with gain of new CA (del13, del17p, t(4;14), t(14;16) or 1q CA when available); (2) 10/115 (9%) patients with loss of a previously identified CA; and (3) 74 patients with no changes. The CA gain group showed a median overall survival of 66 months vs. 84 months in the third group (HR 0.56, 95% CI 0.34-0.92, p = 0.023). Clonal evolution occurs as disease progresses after different chemotherapy lines. Patients who acquired high-risk CA had the poorest prognosis. Our findings highlight the importance of performing FISH analysis both at diagnosis and at relapse.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos/genética , Evolución Clonal , Leucemia de Células Plasmáticas , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple Quiescente , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia de Células Plasmáticas/genética , Leucemia de Células Plasmáticas/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Mieloma Múltiple Quiescente/genética , Mieloma Múltiple Quiescente/mortalidad , Tasa de Supervivencia
6.
Best Pract Res Clin Haematol ; 33(1): 101152, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32139017

RESUMEN

Multiple myeloma, a bone marrow cancer, is preceded by precursor stages called monoclonal gammopathy of unknown significance and smoldering multiple myeloma. Over the past few years, highly effective and safe therapies have been made available to treat multiple myeloma. This represents a major breakthrough and has major therapeutic implications. Treatment for multiple myeloma has evolved to include treatment of precursor stages (early treatment) as these therapies are shown to be safe and effective also in smoldering myeloma. Randomized studies have shown that early treatment can delay the onset of multiple myeloma and even improve overall survival compared to observation in smoldering myeloma. The best therapeutic course and selection of patients with smoldering myeloma to treat is still a matter of debate. In this manuscript, we review the definition, management, clinical implications of smoldering myeloma and early detection of myeloma in the current context and with up-to-date data.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lenalidomida/uso terapéutico , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/diagnóstico , Oligopéptidos/uso terapéutico , Mieloma Múltiple Quiescente/diagnóstico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Médula Ósea/patología , Dexametasona/uso terapéutico , Progresión de la Enfermedad , Esquema de Medicación , Detección Precoz del Cáncer , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Neoplasia Residual , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Mieloma Múltiple Quiescente/tratamiento farmacológico , Mieloma Múltiple Quiescente/mortalidad , Mieloma Múltiple Quiescente/patología , Análisis de Supervivencia
7.
J Clin Oncol ; 38(11): 1126-1137, 2020 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-31652094

RESUMEN

PURPOSE: Observation is the current standard of care for smoldering multiple myeloma. We hypothesized that early intervention with lenalidomide could delay progression to symptomatic multiple myeloma. METHODS: We conducted a randomized trial that assessed the efficacy of single-agent lenalidomide compared with observation in patients with intermediate- or high-risk smoldering multiple myeloma. Lenalidomide was administered orally at a dose of 25 mg on days 1 to 21 of a 28-day cycle. The primary end point was progression-free survival, with disease progression requiring the development of end-organ damage attributable to multiple myeloma and biochemical progression. RESULTS: One hundred eighty-two patients were randomly assigned-92 patients to the lenalidomide arm and 90 to the observation arm. Median follow-up is 35 months. Response to therapy was observed in 50% (95% CI, 39% to 61%) of patients in the lenalidomide arm, with no responses in the observation arm. Progression-free survival was significantly longer with lenalidomide compared with observation (hazard ratio, 0.28; 95% CI, 0.12 to 0.62; P = .002). One-, 2-, and 3-year progression-free survival was 98%, 93%, and 91% for the lenalidomide arm versus 89%, 76%, and 66% for the observation arm, respectively. Only six deaths have been reported, two in the lenalidomide arm versus four in the observation arm (hazard ratio for death, 0.46; 95% CI, 0.08 to 2.53). Grade 3 or 4 nonhematologic adverse events occurred in 25 patients (28%) on lenalidomide. CONCLUSION: Early intervention with lenalidomide in smoldering multiple myeloma significantly delays progression to symptomatic multiple myeloma and the development of end-organ damage.


Asunto(s)
Lenalidomida/uso terapéutico , Mieloma Múltiple Quiescente/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Lenalidomida/efectos adversos , Masculino , Persona de Mediana Edad , Calidad de Vida , Mieloma Múltiple Quiescente/mortalidad
8.
Leuk Lymphoma ; 60(12): 2968-2974, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31169049

RESUMEN

We explore the predictive role of 2014-updated International Myeloma Working Group (IMWG) diagnostic criteria and of some of currently available risk models for progression to symptomatic myeloma when applied in our unselected population of 75 smoldering multiple myeloma (SMM) patients observed between 2000 and 2015. Risk scores including routinely used clinical parameters such as bone marrow plasmacell infiltration rate, immunoparesis, serum monoclonal component (sMC) value, and altered free light chain ratio (FLCr), were clinically useful to identify SMM patients at higher risk of progression. Time to myeloma progression in our ultra-high risk SMM according to IMWG diagnostic update criteria was very short (12.4 months). Our analysis identified as independent reliable predictors of progression altered FLCr as well as increasing plasma cell infiltration which are part of most commonly applied risk models. Waiting for new scoring systems, bone marrow evaluation and complete laboratory screening are still milestones for SMM management.


Asunto(s)
Medición de Riesgo/métodos , Mieloma Múltiple Quiescente/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Biopsia , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Mieloma Múltiple Quiescente/etiología , Mieloma Múltiple Quiescente/mortalidad , Mieloma Múltiple Quiescente/terapia
9.
Clin Cancer Res ; 25(13): 3772-3775, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30890552

RESUMEN

PURPOSE: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma. PATIENTS AND METHODS: In a randomized, double-blind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety. RESULTS: Median age was 62 years (range: 21-84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24-1.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group). CONCLUSIONS: Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Terapia Molecular Dirigida , Mieloma Múltiple Quiescente/tratamiento farmacológico , Mieloma Múltiple Quiescente/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Mieloma Múltiple Quiescente/etiología , Mieloma Múltiple Quiescente/mortalidad , Resultado del Tratamiento , Adulto Joven
12.
Blood Cancer J ; 8(6): 59, 2018 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-29895887

RESUMEN

In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45-72). BMPC% > 20% [hazard ratio (HR): 2.28 (CI, 1.63-3.20); p < 0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11-2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55-2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n = 143); intermediate risk (one of the three risk factors; n = 121); and high risk (≥2 of the three risk factors; n = 153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (p < 0.0001). BMPC% > 20%, M-protein > 2 g/dL, and FLCr > 20 at diagnosis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression.


Asunto(s)
Guías de Práctica Clínica como Asunto , Mieloma Múltiple Quiescente/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Médula Ósea/patología , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Imagen Multimodal , Proteínas de Mieloma , Oportunidad Relativa , Guías de Práctica Clínica como Asunto/normas , Pronóstico , Factores de Riesgo , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/mortalidad
13.
Br J Haematol ; 182(4): 495-503, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29808907

RESUMEN

Smouldering multiple myeloma (SMM) is associated with increased risk of progression to multiple myeloma within 2 years, with no approved treatments. Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in vitro. CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC. In this phase II, non-randomized study (NCT01441973), patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2 weeks thereafter). The primary endpoint was the relationship between baseline proportion of bone marrow-derived CD56dim NK cells and maximal M protein reduction; secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Fifteen patients received 20 mg/kg and 16 received 10 mg/kg; combined data arepresented. At database lock (DBL, September 2014), no association was found between baseline CD56dim NK cell proportion and maximal M protein reduction. With minimum 28 months' follow-up (DBL: January 2016), ORR (90% CI) was 10% (2·7-23·2) and 2-year PFS rate was 69% (52-81%). Upper respiratory tract infections occurred in 18/31 (58%) patients. Four (13%) patients experienced infusion reactions, all grade 1-2. Elotuzumab plus lenalidomide/dexamethasone is under investigation for SMM.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple Quiescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Antígenos CD/sangre , Antígenos CD/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/inmunología , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/tratamiento farmacológico , Mieloma Múltiple Quiescente/inmunología , Mieloma Múltiple Quiescente/mortalidad , Tasa de Supervivencia
14.
Leukemia ; 32(6): 1427-1434, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29463830

RESUMEN

Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1.1 years (95% CI 0.5-2.0) and progression rate at 3 years was 71%. Development of the evolving type drastically worsened the prognostic estimation made at diagnosis for every covariate predictive of progression (serum M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo Clinic risk). On average, the hazard ratio for progression to symptomatic MM increased to 5.1 (95% CI 3.4-7.6) after recognition of the evolving type. In conclusion, in patients with SMM the evolving pattern accurately predicts the risk of early progression to symptomatic disease, thereby allowing the identification of ultra-high risk patients who would be candidates for immediate therapy.


Asunto(s)
Proteínas de Mieloma/análisis , Mieloma Múltiple Quiescente/sangre , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Mieloma Múltiple Quiescente/mortalidad
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