Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Falência Renal Crônica/fisiopatologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/fisiopatologia , Adulto , Idoso , Cloridrato de Bendamustina , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Mostarda Nitrogenada/administração & dosagem , Talidomida/administração & dosagemRESUMO
BACKGROUND: Reduced-intensity conditioning allogeneic transplantation for myeloma is associated with lower non-relapse mortality and higher relapse rates in comparison with myeloablative conditioning transplants. PATIENTS AND METHODS: We have retrospectively audited 19 patients with myeloma or primary plasma cell leukemia who received allogeneic transplantation with a uniform alemtuzumab-based reduced-intensity conditioning protocol. These patients had not been treated with bortezomib or lenalidomide before transplantation. RESULTS: The treatment-related mortality at 1 year was (4/19) 21% with low incidence of graft-versus-host disease (6%) and 2-year progression-free survival and overall survival rates of 35% and 42%, respectively. CONCLUSION: Progression-free survival in this cohort of patients is comparable to previously published data of reduced-intensity conditioning allogeneic transplantation in myeloma. However, there is no plateau observed on the survival curves with a significant transplant-related mortality of 21%. Therefore, alemtuzumab-based allogeneic transplantation cannot be recommended as standard practice outside of clinical trials for treatment of myeloma.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária/terapia , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados , Feminino , Doença Enxerto-Hospedeiro , Humanos , Leucemia Plasmocitária/mortalidade , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1-21 and dexamethasone 20 mg orally days 1-4 and 8-11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial response rate 45% giving an overall response rate of 81%. After 21 months median follow-up, projected 2-year progression-free survival was 56%, with 80% overall survival at 30 months. Ten further patients were treated at MTD with a 40% CR rate. No dose reductions for any study drugs or deaths occurred during cycles 1-9. Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials.
