RESUMEN
BACKGROUND: The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib. METHODS: This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT. RESULTS: A total of 70 patients were included; 30 (42.9%) underwent allogeneic HSCT while 40 (57.1%) received only chemotherapy plus dasatinib. In comparing overall survival (OS) rates, results between the 2 groups were similar with a 1-year OS of 93.3% versus 100% (P = 0.20), 2-year OS of 89.8% versus 86.2% (P = 0.72), and 3-year OS of 76% versus 71.3% (P = 0.56) in the transplant versus nontransplant groups, respectively. The 3-year relapse-free survival (RFS) rates were also similar at 70.5% in the transplant group and 80.1% in the nontransplant group (P = 0.94). Subgroup analyses were performed for patients with specific poor prognostic factors (higher white blood count, older age, positive minimal residual disease status), but results again showed no significant survival difference between transplant and nontransplant patients. CONCLUSIONS: While HSCT has historically led to a survival advantage in Ph+ ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Dasatinib/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug warnings and toxicity management.