RESUMO
From January 1970 to December 2018, 1304 patients were diagnosed with multiple myeloma (MM) at our institution and 256 (19.6%) had plasmacytomas (Ps) (paraskeletal -PPs- 17.6%, extramedullary -EMPs-1.9%). Patients with Ps had lower serum M-protein and less advanced ISS stage than those without. At first relapse, 192 out of 967 patients (19.8%) developed Ps (PPs 14.6%, EMPs 5.1%). The only factor associated with Ps at relapse was the presence of Ps at diagnosis (46% vs 13%, p < 0.00001) with no impact with exposure to novel drugs or previous autologous stem-cell transplantation (ASCT). The median overall survival (OS) was 45, 44 and 20 months for patients without Ps, PPs and EMPs, respectively (p = 0.013). Patients with PPs who underwent ASCT had similar OS than those without Ps (98 vs. 113 months) and significantly longer than those with EMPs (98 vs 47 months, p = 0.006). In patients non-eligible for ASCT the presence of PPs or EMPs was associated with shorter OS compared with patients without Ps (32 vs. 24 vs. 6 months, p = 0.009). In the relapsed setting, a significant survival benefit was observed beyond the year 2000, but still with significant differences among patients without Ps, PPs and EMPs (37 vs 22 vs 16 months, p = 0.003). Importantly, rescue therapy with combinations of proteasome-inhibitors plus immunomodulatory drugs was associated with prolonged OS from first relapse (over 6 years), even in patients with EMPs.
Assuntos
Mieloma Múltiplo , Plasmocitoma , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Plasmocitoma/diagnóstico , Plasmocitoma/terapia , Complexo de Endopeptidases do Proteassoma , Transplante AutólogoRESUMO
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.
Assuntos
Proteínas do Mieloma/análise , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Mieloma Múltiplo Latente/mortalidadeRESUMO
Heat-shock proteins (HSP) are important molecules in the pathogenesis of multiple myeloma (MM). Their blockages by drugs or cellular immune response have been investigated, and a possible association with the presence of oligoclonal bands (OB) has been postulated in patients with MM after allogenic stem cell transplantation. The aim of the present study was to ascertain the serum antibody levels against three HSP (60, 70 and 90) by ELISA in patients with MM in complete remission after autologous stem cell transplantation (ASCT), with or without OB, and compare them with those patients with stable gammopathy of undetermined significance (MGUS) and healthy controls. Our results in samples after ASCT showed no differential levels of anti-HSP according to the presence or absence of the oligoclonal response. However, higher levels of anti-HSP90 were found in patients with stable MGUS in comparison with MM patients (p = 0.004). In the same line, a longer progression-free survival was observed in those patients who presented higher anti-HSP90 levels after ASCT (p = 0.042). These results suggest, for first time, the potential of anti-HSP90 humoral immune response for long-term control of malignant plasma cell disorders.
Assuntos
Anticorpos Antineoplásicos/biossíntese , Autoanticorpos/biossíntese , Autoantígenos/biossíntese , Chaperonina 60/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Choque Térmico HSP90/imunologia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/imunologia , Proteínas de Neoplasias/imunologia , Bandas Oligoclonais/imunologia , Adulto , Idoso , Anticorpos Antineoplásicos/sangue , Anticorpos Antineoplásicos/imunologia , Especificidade de Anticorpos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/sangue , Autoantígenos/imunologia , Ácidos Borônicos/administração & dosagem , Bortezomib , Terapia Combinada , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Bandas Oligoclonais/sangue , Pirazinas/administração & dosagem , Indução de Remissão , Talidomida/administração & dosagem , Transplante AutólogoRESUMO
Limited data has been published on the treatment results in patients with light-chain deposition disease (LCDD). Whenever possible, high-dose melphalan followed by autologous stem cell transplantation (ASCT) has been the first treatment option, achieving somehow better results than conventional therapy. However, and based on the promising results obtained by treating patients with light-chain amyloidosis with bortezomib/dexamethasone, new treatment options appear in LCDD. Herein, we describe three patients with LCDD treated with bortezomib/dexamethasone followed by high-dose melphalan and autologous transplantation. We believe that this new approach should be the treatment of choice in this disease. In addition, those patients achieving hematologic complete response after ASCT could benefit from a kidney transplant if the renal impairment requiring dialysis persists.
Assuntos
Ácidos Borônicos/uso terapêutico , Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Adulto , Ácidos Borônicos/administração & dosagem , Bortezomib , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Pirazinas/administração & dosagemAssuntos
Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos/química , Sistemas de Liberação de Medicamentos/métodos , Drogas em Investigação/química , Humanos , Mieloma Múltiplo/patologia , Indução de Remissão , Resultado do TratamentoRESUMO
Two variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M-protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non-evolving type, with a long-lasting, stable M-protein and longer time to progression. Comparative genomic hybridisation (CGH) analyses in both subtypes of SMM (seven evolving and eight non-evolving SMM) were performed. Evolving SMM showed cytogenetic changes consistent with those found in de novo symptomatic MM (1q gains, chromosome 13 deletions) while the non-evolving variant showed no 1q gains and deletions were uncommon.
Assuntos
Cromossomos Humanos Par 13 , Mieloma Múltiplo/classificação , Proteínas do Mieloma/genética , Exame de Medula Óssea , Aberrações Cromossômicas , Progressão da Doença , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Interfase , Mieloma Múltiplo/genética , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: Thalidomide is an antiangiogenic drug that produces a response rate ranging from 32 to 64% in patients with refractory/relapsed multiple myeloma (MM). However, the efficacy of thalidomide in patients with soft-tissue plasmacytomas is controversial. The aim of this study was to assess the response rate to thalidomide in patients with advanced MM and to correlate the response rate with the presence of extramedullary involvement. DESIGN AND METHODS: Thirty-eight patients with refractory/relapsed MM were treated with thalidomide. Eleven patients had extramedullary involvement when therapy was initiated. The response rate was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation. RESULTS: Sixteen of the 38 patients (42%) responded to thalidomide. The response rate was significantly higher in patients without extramedullary involvement (59% vs 0%, p=0.0006). Although four of the 11 patients with extramedullary involvement had a serological response, a progression of the soft-tissue masses was observed in all of them. INTERPRETATION AND CONCLUSIONS: Thalidomide is effective in patients with advanced MM. However, extramedullary disease does not respond to thalidomide, as delivered in this series. The mechanisms to explain different response to therapy depending on tumor homing warrant further investigation.