RESUMO
We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.
Assuntos
DNA de Neoplasias/genética , Genes Neoplásicos , Mieloma Múltiplo/genética , Análise de Sequência de DNA/métodos , Aberrações Cromossômicas , Cromossomos Humanos Par 17/ultraestrutura , Análise Mutacional de DNA/métodos , Genes p53 , Humanos , Hibridização in Situ Fluorescente , Mutação , RiscoAssuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma , Mieloma Múltiplo , Proteínas de Neoplasias/biossíntese , Peptídeos/administração & dosagem , Tomografia por Emissão de Pósitrons , Receptores CXCR4/biossíntese , Adulto , Idoso , Feminino , Humanos , Linfoma/diagnóstico por imagem , Linfoma/radioterapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/radioterapia , Proteínas de Neoplasias/agonistas , Receptores CXCR4/agonistasAssuntos
Biomarcadores Tumorais/metabolismo , Radioisótopos de Carbono/metabolismo , Metionina/metabolismo , Mieloma Múltiplo , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Estudos ProspectivosAssuntos
Bases de Dados de Ácidos Nucleicos , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Proteínas de Neoplasias/genética , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mieloma Múltiplo/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late-stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five-drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab ("Pom-PAD-Dara") in RRMM. METHODS: We retrospectively analyzed data of 56 patients with RRMM who received Pom-PAD-Dara between September 2016 and May 2019. RESULTS: Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89%) and six (11%) patients, respectively. The overall response rate (ORR) was 78% and we observed partial remission, very good partial remission, and complete remission in 27 (48%), 13 (23%) and four (7%) patients, respectively. Median progression-free survival was 7 months (95% CI, 3.3-10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73%) patients and included neutropenia (n = 28, 50%), anemia (n = 22, 39%), thrombocytopenia (n = 21, 38%), and pneumonia (n = 6, 11%). CONCLUSION: Pom-PAD-Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.