RESUMO
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 (Assuntos
Dexametasona/administração & dosagem
, Ácidos Hidroxâmicos/administração & dosagem
, Mieloma Múltiplo/tratamento farmacológico
, Terapia de Salvação/métodos
, Talidomida/análogos & derivados
, Idoso
, Idoso de 80 Anos ou mais
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Intervalo Livre de Doença
, Feminino
, Humanos
, Lenalidomida
, Masculino
, Pessoa de Meia-Idade
, Mieloma Múltiplo/complicações
, Indução de Remissão
, Terapia de Salvação/efeitos adversos
, Talidomida/administração & dosagem
, Resultado do Tratamento
, Vorinostat
Assuntos
Antineoplásicos , Mieloma Múltiplo , Recidiva Local de Neoplasia , Idoso , Feminino , Humanos , Masculino , Administração Oral , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/efeitos adversos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , VorinostatRESUMO
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.