Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Clorhidrato de Bendamustina/administración & dosificación , Brentuximab Vedotina , Femenino , Humanos , Inmunoconjugados/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at www.clinicaltrials.gov as #NCT01947140.
Asunto(s)
Aminopterina/análogos & derivados , Antibióticos Antineoplásicos/uso terapéutico , Depsipéptidos/uso terapéutico , Antagonistas del Ácido Fólico/uso terapéutico , Linfoma de Células T/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Aminopterina/administración & dosificación , Aminopterina/efectos adversos , Aminopterina/sangre , Aminopterina/uso terapéutico , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Depsipéptidos/administración & dosificación , Depsipéptidos/efectos adversos , Depsipéptidos/sangre , Femenino , Antagonistas del Ácido Fólico/administración & dosificación , Antagonistas del Ácido Fólico/efectos adversos , Antagonistas del Ácido Fólico/sangre , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos CD79/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Mutación , Factor 88 de Diferenciación Mieloide/genética , Adenina/análogos & derivados , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Inmunofenotipificación , Linfoma de Células B Grandes Difuso/diagnóstico , Piperidinas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Recurrencia , Retratamiento , Resultado del TratamientoRESUMEN
Options for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after brentuximab vedotin (Bv) and autologous stem cell transplantation (ASCT) are limited. Immune checkpoint inhibitors (ICI) are active in this population but rarely induce complete response (CR). Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8) or nivolumab (n = 2). Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78%) achieved CR, one partial response, and one reduction of tumor burden. All five patients who had received 5-azacitidine prior to ICI achieved CR, while only two of four who did not receive prior 5-azacitidine achieved CR. At a median follow-up of 9.9 months [0.5-14.3], eight patients are alive and five are still receiving treatment. We documented an unprecedented CR rate after ICI in patients with R/R cHL. We hypothesize that hypomethylating agents might have an immune priming effect and enhance the efficacy of ICI.