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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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In patients with immunoglobulin light-chain (AL) amyloidosis, depth of hematologic response correlates with both organ response and overall survival. Our group has demonstrated that screening with a matrix-assisted laser desorption/ionization-time-of-flight (TOF) mass spectrometry (MS) is a quick, sensitive, and accurate means to diagnose and monitor the serum of patients with plasma cell disorders. Microflow liquid chromatography coupled with electrospray ionization and quadrupole TOF MS adds further sensitivity. We identified 33 patients with AL amyloidosis who achieved amyloid complete hematologic response, who also had negative bone marrow by six-color flow cytometry, and who had paired serum samples to test by MS. These samples were subjected to blood MS. Four patients (12%) were found to have residual disease by these techniques. The presence of residual disease by MS was associated with a poorer time to progression (at 50 months 75% versus 13%, p = 0.003). MS of the blood out-performed serum and urine immunofixation, the serum immunoglobulin free light chain, and six-color flow cytometry of the bone marrow in detecting residual disease. Additional studies that include urine MS and next-generation techniques to detect clonal plasma cells in the bone marrow will further elucidate the full potential of this technique.
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Biomarcadores de Tumor/sangre , Cromatografía Liquida/métodos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Espectrometría de Masas/métodos , Neoplasia Residual/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Masculino , Persona de Mediana Edad , Neoplasia Residual/sangre , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Rarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) (n = 37; years: 2004-2006), cyclophosphamide-Len-Dex (n = 35; years: 2007-2008), and pomalidomide-Dex (n = 29; years: 2008-2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17-150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
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Cadenas Ligeras de Inmunoglobulina/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Non-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study. PATIENTS AND METHODS: This study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: These patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease. CONCLUSIONS: Future multi-institution studies confirming these above findings on this rare entity are warranted.
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Citogenética/métodos , Quimioterapia de Inducción/métodos , Mieloma Múltiple/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
We explored the association between bone marrow plasma cells (BMPCs) and disease presentation and outcome among 1574 AL patients. Three BMPC groups were formulated: <5% (n = 231, 15% of study population), 5-19% (n = 1045, 66%), and ≥20% (n = 298, 19%). Heart and renal involvement were more and less prevalent, respectively, with increasing BMPCs. Patients with ≥20% BMPCs had higher likelihood for classic myeloma phenotype with less skewed lambda restriction, a higher rate of intact immunoglobulin secretion, a lower hemoglobin and higher rates of hypercalcemia and bone lytic lesions. High-risk cytogenetic abnormalities were more common in ≥20% BMPCs. Complete hematological response was less frequent with rising BMPCs. The median survival was inversely associated with the BMPC groups (81, 33, 12 months for <5%, 5-19%, and ≥20% BMPCs, respectively; P < 0.001). Survival discrimination was maintained at 1-year landmark and in those who achieved a complete response. Multivariate analysis accounting for known prognostic markers yielded an independent prognostic role for ≥20% BMPCs, but not for the other BMPC groups. AL patients with 20% or greater BMPCs have poorer outcome independent of their cardiac risk category and stem cell transplant eligibility. Distinct interventions in these patients should be explored to improve outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Células Plasmáticas/patología , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p = .003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p = .001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p = .02) and higher frequency of renal response (100% vs. 68%; p = .005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.
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Citometría de Flujo , Cadenas Ligeras de Inmunoglobulina/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Células Plasmáticas/metabolismo , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaAsunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Fosfatasa Alcalina/metabolismo , Progresión de la Enfermedad , Femenino , Corazón/fisiopatología , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/fisiopatología , Riñón/metabolismo , Riñón/fisiopatología , Hígado/metabolismo , Hígado/fisiopatología , Masculino , Proteinuria/metabolismo , Resultado del TratamientoRESUMEN
Improvement in survival in Light chain (AL) amyloidosis has been seen over recent decades, enabling more patients to achieve long-term survival. Patients with AL amyloidosis who survived ≥10 years from time of diagnosis (n = 186) were the subject of this study. Ten-year survivors represented 22% of the total population. These patients were characterized by favourable patient, organ and plasma cell features. Of note, trisomies were less common among 10-year survivors compared to those who did not survive to 10 years. All-time best haematological response was complete response in 67%, very good partial response in 30%, partial response in 2% and no response in 1%, with 11% having received a consolidative strategy for inadequate response to first line therapy. The overall organ response rate to first-line therapy was 76%, which increased to 86% when considering subsequent line(s) of therapy. Forty-seven percent of the 10-year survivors did not require a second-line therapy. The median treatment-free survival (TFS) among the 10-year survivors was 10·5 years (interquartile range 7·4-12·2). On multivariate analysis independent predictors for TFS were the achievement of complete haematological response and lack of cardiac involvement. Long-term survivors are increasingly seen in AL amyloidosis and present distinct patient, organ and clonal disease features.
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Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Anciano , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Cardiopatías/genética , Cardiopatías/mortalidad , Trasplante de Células Madre Hematopoyéticas , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/genética , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , TrisomíaRESUMEN
The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P < .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.
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Deleción Cromosómica , Cromosomas Humanos Par 17 , Mieloma Múltiple/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , PronósticoRESUMEN
The prognostic significance of novel agent-induced thrombocytopenia in newly diagnosed multiple myeloma (MM) is unknown. We identified 665 newly diagnosed patients receiving proteasome inhibitors and/or immunomodulators with pretreatment platelet counts ≥100,000/µL. Median progression-free survival (PFS) was 1.88 years (95% CI 1.48-2.38) for patients who developed treatment-related thrombocytopenia (<100,000/µL) within sixty days of initiation of first-line therapy, compared to 2.64 years (95% CI 2.39-2.78) in patients who did not (p = .042), while median overall survival (OS) was 5.70 years (95% CI 3.02-9.00) and 8.43 years (95% CI 6.62-9.17), respectively (p = .030). Platelet count reduction >70% from pretreatment baseline was similarly predictive of inferior PFS and OS. This is the first study to demonstrate the predictive and prognostic value of treatment-related thrombocytopenia in newly diagnosed MM.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Trombocitopenia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Biopsia , Análisis Citogenético , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trombocitopenia/diagnósticoRESUMEN
Achievement of a complete response has been associated with improved outcomes in patients with multiple myeloma. Recently, increasing application of minimal residual disease (MRD) assessment has shown that MRD negativity is a powerful prognostic factor for survival outcomes. We wanted to examine the impact of the polyclonal plasma cell (pPC) compartment among patients in complete response (CR) but are MRD positive. This is a retrospective cohort study where 460 myeloma patients were identified who met criteria for CR and had multicolor flow cytometry performed on the bone marrow (BM). Monoclonal and pPCs were estimated during MRD testing. Final outcomes including overall survival (OS) and time to next treatment (TTNT) were compared among the groups. The median OS for the entire cohort was not reached (95% CI; 63 mos, NR) and the median TTNT was 31 months (95% CI; 27,36). Among the MRDneg group, median TTNT was 37.6 months vs 23 months for MRDpos patients (P < .001); the median OS was not reached for either group, but there was a trend toward better survival for MRDneg patients. Among the MRDpos group, median percentage of pPCs was 65% (2.5-98.5), and those with >95% pPCs had a significantly better TTNT (NR vs 23 months; P = .02) and a trend toward better OS. We conclude that achievement of MRD negativity predicts for better response durability and trend toward improved OS and an increased proportion of pPC predicts for better outcomes within those who have residual tumor cells highlighting the importance of marrow normalization.
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Médula Ósea , Mieloma Múltiple , Células Plasmáticas , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Médula Ósea/patología , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Neoplasia Residual/terapia , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We compared the outcomes of 310 patients with newly diagnosed multiple myeloma with del(17p) detected by FISH to patients with high-risk translocations (HRT) (n = 79) and standard-risk (SR) cytogenetics (n = 541). The median progression-free survival (PFS) following initial therapy for the three groups was 21.1, 22, and 30.1 months, respectively (P = 0.437- del(17p) vs. HRT); the median overall survival (OS) was 47.3, 79.1, and 109.8 months, respectively, (P = 0.007- del(17p) vs. HRT). PFS and OS for patients with relative loss of 17p (n = 21) were comparable to other patients with del(17p). The PFS was similar between the del(17p) and HRT groups when stratified for age, ISS stage or treatment. The OS of del(17p) and HRT groups were similar in presence of advanced age, ISS III stage or if patients did not receive a proteasome-inhibitor containing induction. ISS III stage, high LDH and HRT, but not the percentage of cells with del(17p) predicted shorter OS in patients with del(17p). The median OS for low (ISS I, normal LDH and no HRT), intermediate (neither low nor high-risk) and high-risk (ISS III and either elevated LDH or coexistent HRT) groups among del(17p) patients were 96.2, 45.4, and 22.8 months, respectively, allowing further risk stratification.
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Deleción Cromosómica , Cromosomas Humanos Par 17 , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Aberraciones Cromosómicas , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , PronósticoRESUMEN
Despite the absence of high-risk cytogenetics and lower International Staging System (ISS) stages, a subset of patients with multiple myeloma (MM) experience poor overall survival (OS). We studied 1461 patients with newly diagnosed MM to identify patient and disease characteristics that predict a high-risk phenotype among standard-risk patients. Fifty-six percent of all patients presented with standard-risk disease. Among them, advanced age, extremes of body mass index, non-hyperdiploid karyotype and abnormal lymphocyte counts were associated with worse OS. Standard-risk patients with 0-1 of these adverse factors (hazard ratio [HR] 0·32, 95% confidence interval [CI] 0·24-0·43, P < 0·001) and 2 adverse factors (HR 0·54, 95% CI 0·41-0·72, P < 0·001) experienced better OS than high-risk patients. Two or more adverse factors were present in 17% of standard-risk patients and were associated with OS comparable to high-risk patients (HR 0·91, 95% CI 0·67-1·24, P = 0·548). Predictive power among standard-risk patients was improved using score groups compared to ISS stages. Patients with standard-risk MM are a heterogeneous group with one in six patients experiencing OS comparable to high-risk disease. Patients at risk can be identified using readily available patient and disease characteristics. These findings emphasize the importance of accurate risk stratification and help explain part of the heterogeneity observed in clinical practice.
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Mieloma Múltiple/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Índice de Masa Corporal , Femenino , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Estadificación de Neoplasias , Fenotipo , Pronóstico , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
OBJECTIVE: To describe the clinical and laboratory characteristics of patients with meticulously typed light chain (AL) amyloidosis. PATIENTS AND METHODS: Patients (N=592) with biopsy-proven, mass spectrometry-confirmed AL amyloidosis diagnosed from January 1, 2008, through August 31, 2015, were included. RESULTS: The median patient age at diagnosis was 63 years. Thirty-four percent of patients (n=204) had isolated organ involvement, mostly heart (19% [n=115]) followed by kidney (9% [n=53]). In contrast, 25% (n=146) had more than 2 involved organs. Patients with isolated cardiac involvement had similar cardiac dysfunction compared with those with nonisolated cardiac amyloidosis. In contrast, isolated renal involvement was associated with increased proteinuria and higher estimated glomerular filtration rate compared with nonisolated renal amyloidosis. Serum and urine immunofixation electrophoresis results were positive in 80% and 88% of patients, respectively, with 94% of patients having at least 1 positive immunofixation electrophoresis result (serum or urine). The serum free light chain ratio was abnormal in 91% of patients. When all monoclonal protein studies were combined, only 1 patient (0.2%) had normal results. The 1- and 5-year survival rates were 65% and 46%, respectively. Survival of patients with cardiac amyloidosis was not influenced by the number of involved organs (1 vs >1 organ), emphasizing the prognostic significance of cardiac involvement. CONCLUSION: When mass spectrometry is used to definitively type amyloid, only a fraction of a percent of patients with AL have negative monoclonal protein studies, unlike historical reports. Patient characteristics and outcomes of accurately typed patients are described.
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Proteínas Amiloidogénicas/análisis , Cardiopatías/inmunología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/inmunología , Enfermedades Renales/inmunología , Anciano , Cardiomiopatías/inmunología , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/sangre , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Pronóstico , Proteinuria/inmunologíaRESUMEN
Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), or solitary plasmacytoma (SPC). There is a lack of data regarding impact of these pre-existing monoclonal gammopathies (MGs) on MM outcomes. Patients with prior diagnosis of MGUS, SMM, or PC from 1973 to 2015 (cases) were identified from our institution's database and compared to those without a known MG (controls). The primary outcome of interest was overall survival (OS). Multivariate analysis was performed to ascertain factors impacting all-cause mortality. We identified 774 patients with a prior diagnosis of MGUS, SMM or SPC (cases) and a control population (1:2) matched for the year of diagnosis (n = 1548). After a median follow-up of 81 months, the cases showed a longer median OS than the controls (71 months vs. 56 months). The improved OS was limited to those with a known prior diagnosis of SMM (80 months) and SPC (95 months), compared to MGUS (60 months). Multivariable analysis revealed that MM patients with known prior MG had less overall mortality than those without, and this was limited to prior SMM/SPC group (HR 0.68, 95% CI: 0.50-0.93), as compared to the MGUS group (HR 0.83, 95% CI: 0.66-1.05).
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Mieloma Múltiple/epidemiología , Paraproteinemias/epidemiología , Anciano , Biomarcadores , Médula Ósea/patología , Células de la Médula Ósea/patología , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Paraproteinemias/mortalidad , Estudios RetrospectivosRESUMEN
Peripheral blood biomarkers of tumor microenvironment and immune surveillance are independent prognostic factors in multiple myeloma. The timing and prognostic impact of immune reconstitution has been studied after autologous hematopoietic stem cell transplantation, less is known about its significance in newly diagnosed multiple myeloma. We studied absolute lymphocyte (ALC) and absolute monocyte (AMC) counts at the time of treatment initiation and 1 month thereafter in 771 newly diagnosed patients. Two hundred and thirty-four patients (31%) had evidence of immune dysregulation at baseline (abnormal biomarkers). Eighty-seven of these patients (37%) recovered normal biomarkers at 1 month (early immune reconstitution). The absence of immune dysregulation at baseline (compared to the presence thereof) was associated with better overall survival (HR 0.77, 95% CI 0.61-0.97, P = 0.025, n = 771). The absence of immune dysregulation at 1 month (compared to the persistence or development thereof) was associated with better overall survival (HR 0.63, 95% CI 0.50-0.80, P < 0.001, n = 771). Early immune reconstitution (compared to the persistence or development of immune dysregulation) was associated with better overall survival (HR 0.62, 95% CI 0.43-0.92, P = 0.016, n = 771). Cytogenetic high-risk disease was negatively, and treatment with immunomodulators positively, associated with early immune reconstitution. The presence or development of immune dysregulation in newly diagnosed multiple myeloma is an independent risk factor. The favorable impact of early immune reconstitution suggests immune dysregulation to be a potentially modifiable risk factor that may be exploited for therapeutic benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Factores Inmunológicos/uso terapéutico , Mieloma Múltiple/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Bortezomib/uso terapéutico , Ciclofosfamida/uso terapéutico , Análisis Citogenético , Dexametasona/uso terapéutico , Femenino , Humanos , Reconstitución Inmune , Lenalidomida/uso terapéutico , Recuento de Leucocitos , Linfocitos/inmunología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/patología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Trasplante AutólogoAsunto(s)
Biomarcadores/sangre , Cadenas Ligeras de Inmunoglobulina/sangre , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/sangre , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Overall survival (OS) of multiple myeloma has improved remarkably over time, with the recent Intergroupe Francophone du Myelome (IFM) 2009 randomized trial reporting a 4-year OS rate of approximately 82% in patients receiving modern therapy. However, survival estimates from clinical trials may overestimate outcomes seen in clinical practice even with the adjustment for age and other key characteristics. The purpose of this study was to determine the OS of myeloma patients seen in routine clinical practice who resembled the cohort studied in the IFM 2009 trial. A second goal was to conduct a brief comparative effectiveness analysis of bortezomib, lenalidomide, dexamethasone, and other major induction regimens used during the study period. We studied all patients with myeloma 65 years of age and younger, seen at the Mayo Clinic between January 1, 2010 and August 31, 2015, who had a stem cell harvest performed within 12 months of initial diagnosis. Patients with baseline serum creatinine >2 mg/dL were excluded. Five hundred and eighteen patients were studied. The 4-year OS rate was 82.3%, comparable to results achieved in the contemporaneous IFM randomized trial. The 4-year OS rates for standard and high-risk myeloma were 86.3% and 68.2%, respectively.
Asunto(s)
Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Terapia Combinada , Femenino , Pruebas Genéticas , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Pronóstico , Análisis de Supervivencia , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
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.