RESUMEN
Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Rituximab/efectos adversos , Esteroides/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Glucocorticoides/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Metilprednisolona/efectos adversos , Osteonecrosis/diagnóstico por imagen , Huesos Pélvicos/diagnóstico por imagen , Adulto , Bleomicina/administración & dosificación , Estudios Transversales , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Glucocorticoides/administración & dosificación , Enfermedad de Hodgkin/epidemiología , Humanos , Incidencia , Masculino , Metilprednisolona/administración & dosificación , Osteonecrosis/inducido químicamente , Osteonecrosis/epidemiología , Huesos Pélvicos/efectos de los fármacos , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
To evade elimination by the host immune system, tumor cells commonly exploit physiological immune checkpoint pathways, restraining efficient anti-tumor immune cell function. Growing understanding of the complex dialog between tumor cells and their microenvironment contributed to the development of immune checkpoint inhibitors. This innovative strategy has demonstrated paradigm-shifting clinical activity in various malignancies. Antibodies targeting programmed death 1 and cytotoxic T-lymphocyte-associated protein-4 are also being investigated in lymphoid malignancies with varying levels of activity and a favorable toxicity profile. To date, evaluated only in the setting of relapsed or refractory disease, anti-programmed death 1 antibodies such as nivolumab and pembrolizumab show encouraging response rates particularly in classical Hodgkin lymphoma but also in follicular lymphoma and diffuse-large B-cell lymphoma. As the first immune checkpoint inhibitor in lymphoma, nivolumab was approved for the treatment of relapsed or refractory classical Hodgkin lymphoma by the Food and Drug Administration in May 2016. In this review, we assess the role of the pathways involved and potential rationale of checkpoint inhibition in various lymphoid malignancies. In addition to data from current clinical trials, immune-related side effects, potential limitations and future perspectives including promising combinatory approaches with immune checkpoint inhibition are discussed.
Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Inmunomodulación/efectos de los fármacos , Linfoma/tratamiento farmacológico , Terapia Molecular Dirigida , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/metabolismo , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Humanos , Linfoma/diagnóstico , Linfoma/inmunología , Linfoma/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de Señal/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Resultado del TratamientoAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Nivolumab/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Autoinjertos , Supervivencia sin Enfermedad , Eosinófilos , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasibility and toxicity in phase II trials. The introduction of brentuximab vedotin-based regimens led to a paradigm shift in first- and further-line treatment of elderly Hodgkin lymphoma patients, providing adequate disease control within a broader patient population. As far as checkpoint inhibitors are concerned, we are only just beginning to understand the role in the treatment of this population. In relapsed/refractory settings there are few options, ranging from autologous stem cell transplantation in selected patients to pembrolizumab, but unfortunately, palliative care is the most common modality. Importantly, published studies are frequently burdened with numerous biases (such as low numbers of patients, selection bias and lack of geriatric assessment), leading to low level of evidence. Furthermore, there are few ongoing studies on this topic. Thus, elderly Hodgkin lymphoma patients are hard to treat and represent an unmet need in hematologic oncology. In conclusion, treatment needs to be personalized and tailored on a case-by-case basis. In this article, we outline treatment options for elderly Hodgkin lymphoma patients.