Asunto(s)
Antineoplásicos , Mieloma Múltiple , Recurrencia Local de Neoplasia , Anciano , Femenino , Humanos , Masculino , Administración Oral , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: To report the clinicopathologic features of monotypic immunoglobulin G4+ (IgG4+) lymphoid and plasmacytic proliferations. METHODS: Cases were identified from the pathology files. Pathology and clinical materials were reviewed. RESULTS: Eleven cases of monotypic IgG4+ proliferations were identified at nodal, orbital, or salivary sites. Six cases (three men, three women; age, 57-94 years) met criteria for lymphoma or plasma cell neoplasia. Most contained frequent Mott cells. Five cases (three men, two women; age, 40-80 years) had restricted proliferations of atypical/monotypic IgG4+ plasma cells in a background of reactive lymphoid hyperplasia or inflammation. CONCLUSIONS: Monotypic IgG4+ proliferations include lymphomas, plasmacytic neoplasms, and a previously uncharacterized group of proliferations not meeting criteria for conventional hematolymphoid neoplasia. Distinct features included prominent Mott cells and/or monotypic plasma cells within follicles. The proliferations were infrequently associated with IgG4-related disease (IgG4-RD). Our findings raise questions regarding the relationship between clonal IgG4+ proliferations, reactive/inflammatory processes, and IgG4-RD.
Asunto(s)
Inmunoglobulina G , Linfoma/patología , Neoplasias de Células Plasmáticas/patología , Células Plasmáticas/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma/inmunología , Masculino , Persona de Mediana Edad , Neoplasias de Células Plasmáticas/inmunología , Células Plasmáticas/inmunologíaRESUMEN
Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (Asunto(s)
Dexametasona/administración & dosificación
, Ácidos Hidroxámicos/administración & dosificación
, Mieloma Múltiple/tratamiento farmacológico
, Terapia Recuperativa/métodos
, Talidomida/análogos & derivados
, Anciano
, Anciano de 80 o más Años
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Supervivencia sin Enfermedad
, Femenino
, Humanos
, Lenalidomida
, Masculino
, Persona de Mediana Edad
, Mieloma Múltiple/complicaciones
, Inducción de Remisión
, Terapia Recuperativa/efectos adversos
, Talidomida/administración & dosificación
, Resultado del Tratamiento
, Vorinostat
RESUMEN
Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m(2) ; 30-min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1-21), vorinostat (300 or 400 mg; days 1-7, 15-21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28-d cycles. No dose-limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m(2) , lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.