RESUMEN
BACKGROUND: To compare safety and efficacy of ICIs among patients<80 and those ≥80 years of age. METHODS: A single-center retrospective observational cohort study comparing patients<80 and ≥80 years of age matched for cancer site (lung vs others) and participation in a clinical trial. PRIMARY ENDPOINT: grade ≥2 toxicity during the first three months of ICI therapy. The two groups were compared using univariate and multivariate regression. RESULTS: Two hundred and ten consecutive patients were recruited, with the following characteristics: mean age: 66.5±16.8, 20% aged ≥80 years, 75% male, 97% ECOG-PS ≤ 2, 78% G8-index ≤ 14/17, 80% lung or kidney cancer, and 97% metastatic cancer. The grade ≥2 toxicity rate during the first three months of ICI therapy was 68%. Patients aged ≥80 years of age had a more significant (P<0.05) proportion of grade ≥2 non-hematological toxicities (64% vs 45%) than those aged<80 years: rash (14% vs 4%), arthralgia (7.1% vs 0.6%), colitis (4.7% vs 0.6%), cytolysis (7.1% vs 1.2%), gastrointestinal bleeding (2.4% vs 0%), onycholysis (2.4% vs 0%), oral mucositis (2.4% vs 0%), psoriasis (2.4% vs 0%), or other skin toxicities (25% vs 3%). Efficacy among patients ≥80 and<80 years of age was comparable. CONCLUSIONS: Although non-hematological toxicities affected 20% more patients aged ≥80 years, hematological toxicities and efficacy were comparable between patients aged ≥80 and<80 years with advanced cancer and treated with ICIs.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios Retrospectivos , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Observacionales como AsuntoRESUMEN
The understanding of the immune system and the discovery of the proteins and processes involved in its regulation have enabled the emergence of new approaches against cancer. The development of antibodies (immune checkpoint inhibitors) able of blocking interactions that suppress the activation of T cells or their effector actions against cancer cells has modified the prognosis of several cancer forms. Bispecific antibodies as well as cellular immunotherapies (CARs/TILs) are new immunotherapy approaches that have already shown their effectiveness in certain onco-haematological diseases. Unfortunately, only a fraction of treated patients derives benefit from these treatments. The future challenge will be to understand the resistance mechanisms to immunotherapies so that treatment may be personalized for each patient.
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Anticuerpos , Inmunoterapia , HumanosRESUMEN
Use of checkpoint inhibitors to treat cancer was one of the most important revolution these last years and an increasing number of new types of tumors is currently under investigation with these new treatments. However, immune-related adverse events associated with these agents frequently affect various organs, mimicking auto-immune or inflammatory diseases. Some of these effects can be severe, often requiring hospitalization and specialized treatment (immunosuppression). Most known agents are ipilimumab (anti-CTLA-4 antibody) nivolumab and pembrolizumab (anti-PD-1 antibodies). New molecules are now approved or in development as anti-PD-L1 antibodies, anti-LAG-3 or anti-TIM-3 antibodies, increasing the probability and new description of immune-related adverse events. With his experience in auto-immune diseases, the immunologist/internal medicine specialist has an important role in the management of these toxicities. The goal of this review is to focus on the incidence, diagnostic assessment and recommended management of the most relevant immune-related adverse events.
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Antineoplásicos Inmunológicos/efectos adversos , Antígeno CTLA-4/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Antineoplásicos Inmunológicos/farmacología , Enfermedades Autoinmunes/complicaciones , Cardiotoxicidad/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Erupciones por Medicamentos/etiología , Enfermedades Hematológicas/inducido químicamente , Humanos , Enfermedades Renales/inducido químicamente , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Linfáticas/complicaciones , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades Reumáticas/inducido químicamente , Timo , Enfermedades de la Tiroides/inducido químicamenteRESUMEN
INTRODUCTION: Anti-tumoral immunotherapy is currently the basis of a profound modification of therapeutic concepts in oncology, in particular since the arrival of immune checkpoint inhibitors (ICI). In addition to their efficacy profile, these immune-targeted agents also generate adverse events. With the increasing use of ICI for a growing number of tumor types, awareness of immunotherapy-related adverse events is essential to ensure prompt diagnosis and effective management of these potentially serious adverse events. BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (irAEs), which resemble autoimmune disease. Though severe irAEs remain rare, they can be fatal if not diagnosed and treated in an appropriate manner. OUTLOOK AND CONCLUSION: Additional studies are needed to better understand the clinical characteristics and chronology of these adverse effects and to clarify their pathophysiological mechanisms.