RESUMEN
The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.
Asunto(s)
Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida , Quimioterapia de Mantención , Masculino , Melfalán/efectos adversos , Persona de Mediana Edad , Prednisona , Talidomida/efectos adversos , Resultado del Tratamiento , Privación de TratamientoRESUMEN
This case involves a man with a medical history of multiple myeloma and osseous metastasis of prostate carcinoma. He presented with a progressively growing red tumor on his chest for the past three weeks. Histopathological examination revealed many atypical CD0138-positive plasmablastic cells, which matches a cutaneous manifestation of multiple myeloma.
Asunto(s)
Mieloma Múltiple , Neoplasias de la Próstata , Enfermedades de la Piel , Neoplasias Cutáneas , Masculino , Humanos , Neoplasias Cutáneas/patología , Mieloma Múltiple/diagnóstico , Esternón/patología , Neoplasias de la Próstata/patologíaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Evaluación Geriátrica/métodos , Mieloma Múltiple/mortalidad , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVES: We assessed direct health care costs associated with the most commonly prescribed treatments for indolent follicular non-Hodgkin's lymphoma (FL). DESIGN AND METHODS: New and previously diagnosed FL patients (>or=18 years) known during 1997-1998 to 15 Dutch hospitals were selected for inclusion. Each patient was followed for 3 years, and resource use associated with each of the treatments, including watchful waiting, was recorded. The hospital perspective was adopted. Unit costs were based on 2003 price levels. RESULTS: Two hundred patients were included of whom 75% underwent one or more treatments during the 3-year data collection period [25% were not treated because of a watchful waiting strategy (10%) or complete remission (15%)]. Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean (median) per patient cost of 45,326 euro(44,237; n=7) and 18,866 euro (16,532; n=9), respectively (up to discharge only). Intravenous fludarabine cost 10,651 euro (9,995; n=33), rituximab (10,628 euro; 10,124; n=7), and CHOP 7,547 euro (5,833; n=42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for cylophosphamide, vincristine and prednisone of 5,268 euro (2,644; n=58), for radiotherapy of 4,218 euro (4,313; n=52), and for chlorambucil of 2,476 euro (1,098; n=53). INTERPRETATION AND CONCLUSIONS: This study presents information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning, given the high costs of new treatment modalities.
Asunto(s)
Linfoma Folicular/economía , Linfoma Folicular/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/economía , Costos y Análisis de Costo/economía , Femenino , Costos de la Atención en Salud , Costos de Hospital , Humanos , Linfoma Folicular/epidemiología , Linfoma no Hodgkin/economía , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Retrospectivos , Trasplante de Células Madre/economíaRESUMEN
Resistance to chemotherapy in therapy-refractory diffuse large B-cell lymphomas (DLBCL) is related to inhibition of the intrinsic apoptosis pathway. Human soluble tumour necrosis factor (TNF)-related apoptosis-inducing ligand (hsTRAIL/Apo2L) induces apoptosis via the alternative, death-receptor mediated apoptosis pathway and might be an effective alternative form of therapy for these lymphomas. This study investigated whether hsTRAIL/Apo2L could actually induce apoptosis in isolated lymphoma cells of DLBCL biopsies of patients with chemotherapy-refractory DLBCL. Twelve out of a total of 22 DLBCL samples were sensitive to hsTRAIL/Apo2L. These sensitive lymphomas included seven clinically chemotherapy-refractory lymphomas. Furthermore, hsTRAIL/Apo2L induced apoptosis in DLBCL cells and in B-cell lines that showed high expression levels of inhibitors of the intrinsic apoptosis pathway: Bcl-2 and/or X-linked inhibitor of apoptosis (XIAP). hsTRAIL/Apo2L-sensitive lymphoma cells showed expression of the TRAIL receptors R1 and/or R2 and absence of R3 and R4. We conclude that hsTRAIL/Apo2L induced apoptosis in a subpopulation of chemotherapy-refractory nodal DLBCL and that disruption of the intrinsic apoptosis-mediated pathway and expression of Bcl-2 and XIAP did not confer resistance to hsTRAIL/Apo2L-induced apoptosis in DLBCL. Thus, based on our results, further exploration of hsTRAIL/Apo2L as an alternative treatment for patients with chemotherapy-refractory DLBCL should be considered.