Assuntos
Vacina de mRNA-1273 contra 2019-nCoV/administração & dosagem , Vacina BNT162/administração & dosagem , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To evaluate safety and activity of perifosine and sorafenib combination therapy in patients with lymphoproliferative diseases. EXPERIMENTAL DESIGN: Patients with relapsed and refractory lymphoproliferative diseases received perifosine (50 mg twice daily) for 1 month. Patients achieving less than partial response (PR) after perifosine alone were administered the combination therapy [perifosine plus sorafenib (400 mg twice daily)] until progressive disease (PD) or unacceptable toxicity occurred. The pERK and pAKT in peripheral blood lymphocytes as well as serum cytokine levels were investigated as predictive biomarkers of response. RESULTS: Forty patients enrolled in this study. After 1 month of perifosine alone, 36 who achieved less than PR went on to combination therapy, whereas four patients with chronic lymphocytic leukemia (CLL) who achieved PR continued with perifosine alone for a median of 10 months (range, 4-21). The most common drug-related toxicities were grade 1-2 anemia (17%), thrombocytopenia (9%), diarrhea (25%), joint pain (22%), and hand-foot skin reaction (25%). Three patients experienced grade 3 pneumonitis. Eight patients (22%) achieved PR, 15 (42%) achieved stable disease, and 13 (36%) experienced PD. A 28% PR rate was recorded for 25 patients with Hodgkin lymphoma. Among all patients, median overall survival and progression-free survival were 16 and 5 months, respectively. Early reductions in pERK and pAKT significantly correlated with the probability of clinical response. CONCLUSIONS: Perifosine and sorafenib combination therapy is feasible with manageable toxicity and demonstrates promising activity in patients with Hodgkin lymphoma. The predictive value of pERK and pAKT should be confirmed in a larger patient cohort.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Biomarcadores/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Fosforilcolina/administração & dosagem , Fosforilcolina/análogos & derivados , Proteínas Proto-Oncogênicas c-akt/metabolismo , Recidiva , Sorafenibe , Resultado do Tratamento , Adulto JovemRESUMO
In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).