RESUMO
BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.
Assuntos
Colite , Inibidores de Checkpoint Imunológico , Humanos , Masculino , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Colite/induzido quimicamente , Seguimentos , Europa (Continente)RESUMO
Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer.
Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Neoplasias , Infecções Pneumocócicas , Adulto , Humanos , SARS-CoV-2 , Influenza Humana/complicações , Estudos Prospectivos , Estações do Ano , COVID-19/prevenção & controle , COVID-19/complicações , Neoplasias/complicações , Neoplasias/terapia , Vacinação , Infecções Pneumocócicas/complicaçõesRESUMO
BACKGROUND: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated. PATIENTS AND METHODS: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA). RESULTS: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy. CONCLUSIONS: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.
Assuntos
COVID-19 , Neoplasias , Vacinas Virais , Humanos , Vacinas contra COVID-19/farmacologia , Vacina BNT162 , Estudos Longitudinais , Anticorpos Antivirais , Vacinas Virais/genética , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Imunoglobulina G , Imunidade Celular , Neoplasias/tratamento farmacológico , Oxigênio , Vacinas de mRNARESUMO
Herpes zoster (HZ) is the infectious reactivation of the varicella-zoster virus. HZ is more frequent in immunocompromised subjects, including patients with cancer. HZ complications can even last for years with a consequent delay in treatment of the underlying malignancy and with an unfavorable impact on quality of life. Nowadays, HZ is a vaccine-preventable disease: the recent approval of adjuvanted glycoprotein E-based recombinant zoster vaccine has changed preventive perspectives in immunocompromised subjects. Recombinant zoster vaccine induced both strong humoral and cellular immune responses also in immunocompromised patients. The question is, therefore, to which categories of cancer patients we should recommend HZ vaccination. Based on a careful review of the available data present in the literature, including recommendations and expert opinions, we report the position of the Associazione Italiana di Oncologia Medica on HZ vaccination in adult patients with solid tumors, thus providing clinical practice advice in a field where clear-cut information is missing.
Assuntos
Vacina contra Herpes Zoster , Herpes Zoster , Neoplasias , Herpesvirus Humano 3 , Humanos , Qualidade de Vida , VacinaçãoRESUMO
BACKGROUND: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. PATIENTS AND METHODS: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. RESULTS: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). CONCLUSIONS: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity.
Assuntos
COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunoglobulina G/uso terapêutico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.
Assuntos
Antígeno B7-H1 , Vacina BNT162 , COVID-19 , Inibidores de Checkpoint Imunológico , Neoplasias , Receptor de Morte Celular Programada 1 , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Vacina BNT162/administração & dosagem , Vacina BNT162/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Seguimentos , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/imunologia , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , SARS-CoV-2/imunologiaRESUMO
BACKGROUND: Very few cancer patients were enrolled in coronavirus disease-2019 vaccine studies. In order to address this gap of knowledge, real-world studies are mandatory. The aim of this study was to assess both humoral and cellular response after a messenger RNA vaccination schedule. PATIENTS AND METHODS: Eighty-eight consecutive cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary endpoint was the evaluation of the percentage of participants showing a significant increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells, measured by an enzyme-linked immunospot assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval. RESULTS: In SARS-CoV-2-naïve subjects, spike-specific T-cell response was almost undetectable at T0 [median 0.0 interferon-γ (IFN-γ) spot forming units (SFU)/million peripheral blood mononuclear cell (PBMC) interquartile range (IQR) 0-7.5] and significantly increased at T1 and T2 (median 15.0 IFN-γ SFU/million PBMC, 25th-75th 0-40 versus 90 IFN-γ SFU/million PBMC, 25th-75th 32.5-224, respectively) (P < 0.001). Focusing on naïve and experienced SARS-CoV-2 subjects, no differences were reported both in terms of CD4- and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless of previous SARS-CoV-2 exposure. The level of SARS-CoV-2 neutralizing antibodies was low at T1 in SARS-CoV-2-naïve subjects [median 1 : 5 (IQR 1 : 5-1 : 20)] but reached a significantly higher median of 1 : 80 (25th-75th 1 : 20-1 : 160) at T2 (P < 0.0001). Moreover, no COVID-19 cases were documented throughout the period of study. CONCLUSIONS: Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless of the type of cancer and/or the type of immune checkpoint inhibitors.
Assuntos
COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , Estudos de Coortes , Humanos , Inibidores de Checkpoint Imunológico , Leucócitos Mononucleares , Estudos Longitudinais , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , SARS-CoV-2RESUMO
This study provides insights about the diversity, prevalence and distribution of alpine wild galliformes gastrointestinal parasite community, trying to fill a gap in the scientific information currently available in scientific literature. The analysis included three host species: 77 rock partridge (Alectoris graeca saxatilis), 83 black grouse (Tetrao tetrix tetrix) and 26 rock ptarmigan (Lagopus muta helveticus) shot during the hunting seasons 2008-2015. Parasites isolated were Ascaridia compar, Capillaria caudinflata and cestodes. The rock ptarmigan was free from gastrointestinal parasites, whereas the most prevalent helminth (37%) was A. compar in both black grouse and rock partridge. C. caudinflata occurrence was significantly higher in black grouse (prevalence = 10%, mean abundance = 0.6 parasites/sampled animal) than in rock partridge (prevalence = 1.20%, mean abundance = 0.01 parasites/sampled animal). Significant differences were detected among hunting districts. A. compar was found with a significant higher degree of infestation in the hunting districts in the northern part of the study area whereas cestodes abundance was higher in Lanzo Valley. Quantitative analysis of risk factors was carried out using a generalized linear model (GLM) only on the most common parasite (A. compar). Latitude was the only factors associated with infestation risk (OR = 52.4). This study provides information on the composition and variability of the parasite community in the alpine Galliformes species.