RESUMEN
BACKGROUND: The increasing incidence of diffuse large B-cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co-morbidity, frailty, and reduced organ and physiological reserve contribute to treatment-related complications. The optimal dose intensity of R-CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. OBJECTIVES AND METHODS: We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009-2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. RESULTS: Porgression-free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70-79 years (P < 0.001). In contrast, 2-year cumulative relapse incidence, when accounting for non-relapse mortality as a competing risk, was no different between 70-79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS-G: 0-6 vs. >6) (P = 0.27). In 70-79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70-79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). CONCLUSION: 'R-mini-CHOP' provides adequate lymphoma-specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Incidencia , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Prednisona/administración & dosificación , Recurrencia , Estudios Retrospectivos , Rituximab/administración & dosificación , Resultado del Tratamiento , Vincristina/administración & dosificaciónAsunto(s)
Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/mortalidad , Vigilancia de la Población , Estadística como Asunto/tendencias , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Sistema de Registros , Tasa de Supervivencia/tendencias , Resultado del TratamientoAsunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Linfoma de Células T Periférico/complicaciones , Trastornos Linfoproliferativos/diagnóstico , Antineoplásicos/uso terapéutico , Diagnóstico Diferencial , Infecciones por Virus de Epstein-Barr/diagnóstico , Resultado Fatal , Genoma Viral , Enfermedad Injerto contra Huésped/inmunología , Humanos , Enfermedades Linfáticas/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Recurrencia , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversosRESUMEN
BACKGROUND: Small series suggest retreatment of indolent lymphomas with murine anti-CD20 radioimmunotherapy is effective. The longer half-life of iodine-131 ((131)I)-rituximab may result in increased bone marrow exposure, with greater toxicity on repeat administration. We examined the effects of a second (131)I-rituximab in patients with indolent lymphoma following relapse. PATIENTS AND METHODS: We analyzed two institutional databases from January 2000 to July 2007 for retreatment with (131)I-rituximab. The severity of cytopenia, development of myelodysplasia (MDS), acute myeloid leukemia (AML) and hypothyroidism was noted. We compared response duration and toxicity of the treatments. RESULTS: Fourteen of 16 patients responded with nine complete responses (CRs), with a median duration of 10.5 months in responders. Six of 13 reresponders had the same or a longer response and six more remain in complete response. The median event-free survival was not significantly different for the two treatments. There was no significant difference in the severity of myelosuppression. Four patients developed hypothyroidism with three requiring thyroxine. One patient developed AML, with no other cases of MDS. The actuarial progression-free survival rate at 12 months was 36%. CONCLUSIONS: Repeat (131)I-rituximab induces high response rates, some of which result in durable remissions in patients who had previously responded.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Linfoma de Células B/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioinmunoterapia/métodos , Adulto , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/inmunología , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Linfoma de Células B/inmunología , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Probabilidad , Retratamiento , Estudios Retrospectivos , Medición de Riesgo , Rituximab , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Recuento de Linfocitos , Linfoma/inmunología , Linfoma/radioterapia , Radioinmunoterapia , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Humanos , Radioisótopos de Yodo/uso terapéutico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Rituximab , Resultado del TratamientoRESUMEN
Two commonly used chemotherapy regimens for lymphoma salvage therapy were compared: ICE (ifosphamide, carboplatin and etoposide) +/- rituximab and IVE (ifosfamide, epirubicin and etoposide) +/- rituximab, for their efficacy in mobilising peripheral blood stem cells for autologous transplantation. Significant differences were observed between the cohorts in terms of number of patients mobilising the stipulated minimum >2 x 10(6) CD34+/kg (99.2% in IVE group versus 83% in ICE group: P = 0.0002) and also in terms of the number of patients achieving the predetermined target of >5 x 10(6) CD34+/kg, both in total and during the first apheresis procedure (72% in IVE versus 51% in ICE group and 49% in IVE versus 7% in ICE group: P = 0.02 and P < 0.0001 respectively). This analysis of two similar groups of patients treated within a single-centre appears to demonstrate that the IVE regimen is a more effective stem cell mobilisation regimen than ICE in the context of salvage therapy for Hodgkin and non-Hodgkin lymphoma, allowing more patients to achieve the target CD34+ cell collection and proceed to high-dose therapy and autologous stem cell transplantation.