Asunto(s)
Leucemia Linfocítica Crónica de Células B , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Resultado del Tratamiento , Vidarabina/análogos & derivados , Vidarabina/uso terapéuticoRESUMEN
In 2014, an interim analysis of a phase 3 study was performed to evaluate the effectiveness of ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukaemia (BFR CLL) as compared to physician's choice. The five-year follow-up of this phase 3 trial showed that ofatumumab therapy resulted in a numerically but not significantly longer overall survival. As only few patients had the chance to receive a kinase inhibitor later, the study displays the survival of BFR CLL patients in the period prior to receiving small-molecule inhibitors. Ofatumumab is a well-tolerable treatment option in multiresistant advanced CLL.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Vidarabina/farmacología , Vidarabina/uso terapéuticoRESUMEN
In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC (hazard ratio = 0.67; 95% confidence interval, 0.51-0.88; p = .0032). Grade ≥3 adverse events (≤60 days after last dose) were reported in 134 (74%) OFA + FC-treated patients compared with 123 (69%) FC-treated patients. Of these, neutropenia was the most common (89 [49%] vs. 64 [36%]). OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone, thus providing an alternative treatment option for patients with relapsed CLL. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00824265).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Recurrencia , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up. The two treatment arms were not significantly different at the nominal 0.05 level for GHS/HRQoL (p = .7278) or B symptoms (p = .5968). Small improvements in quality of life were maintained after therapy. The addition of ofatumumab was without any adverse impact on HRQoL (NCT00824265).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Calidad de Vida , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Recurrencia , Vidarabina/análogos & derivadosRESUMEN
We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5.4 months, physicians' choice: 3.6 months; p = 0.27), median PFS by investigators was significantly longer for ofatumumab versus physicians' choice (7.0 versus 4.5 months; p = 0.003) as was time to next therapy (median 11.5 versus 6.5 months; p = 0.0004). PFS and time to next therapy were significantly longer with ofatumumab extended treatment than observation (p = 0.026 and p = 0.002, respectively; n = 37). The adverse-event profile of long-term ofatumumab administration showed no unexpected findings (Clinicaltrials.gov identifier: NCT01313689).