We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP).
From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP ...afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination timepoint (TP) 0, and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose.
Patients characteristics: median age 62 (range, 21-97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG >15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63-9.99;
= 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively.
BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.
Background
The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older.
Objective
The aim of this observational study was to evaluate safety and efficacy of ...vaccine in patients affected by primary brain tumor (PBT).
Methods
We proposed COVID-19 vaccine to all patients affected by PBT followed by Neuroncology Unit of National Cancer Institute Regina Elena.
Results
102 patients received the first dose, 100 the second, and 73 patients received the booster dose. After first dose, we observed one patient with fever and severe fatigue, while after the second one, we recorded adverse events in ten patients. No correlation was observed between adverse events and comorbidities.
Conclusions
The COVID-19 vaccine is safe and well tolerated in PBT patients.
Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative ...malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose.
Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher' exact test and the Mann-Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively.
At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed.
BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).
Objective
Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received ...prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence.
Methods
For the observational, retrospective study, data were collected from five Italian hospital centres that prescribed palbociclib between April 2017 and April 2020. Each centre provided data derived from an administrative database of adult patients treated with palbociclib for the two therapeutic indications.
Treatment adherence was calculated using the proportion of days covered method while time-to-treatment discontinuation was defined as the difference between the first and last date treatment was administered plus the days ideally covered by the last date treatment was given.
Results
There were 375 patients enrolled during the study period, of whom 159 were treated with palbociclib and aromatase inhibitor and 216 were treated with palbociclib and fulvestrant. The time-to-treatment discontinuation was 8.9 months in the case of P + f (95% CI: 7.1−12.7) and 13.7 months in the case of P + ia (95% CI: 8.9−17.5). In both cohorts, treatments that received at least one dose reduction had a statistically higher time-to-treatment discontinuation than those without dose reduction (17.7 months vs. 9.2 and 16.6 vs. 7.4).
The mean adherence in our study was 0.9 and remained high in treatments with one dose reduction (0.83) and this with two dose reductions (0.87).
Conclusion
Based on these findings, it appears that the management of toxicities through reducing doses, as required by the Summary of Product Characteristics, results in a better outcome in terms of therapy duration, and therefore time to failure due to progression or toxicity.
The aim of this study was to analyze real-life data from a cohort of adult patients receiving atezolizumab in combination with carboplatin and etoposide for first-line treatment of ES-SCLC, in order ...to assess relative dose intensity (RDI), time-to-treatment discontinuation (TTD), time-to-treatment failure (TTF), progression-free survival (PFS), overall survival (OS) of treatments as well as the correlation between these outcomes.
An observational retrospective study was conducted. All patients treated with atezolizumab combined with carboplatin and etoposide for first-line treatment of ES-SCLC were included. Median TTD, TTF, PFS and OS were calculated in our cohort of patient by the Kaplan Meier method.
The curves obtained with the Kaplan Meier method of TTF and TTD are substantially similar, indicating a good concordance of the information extracted by the two different data sources. This tendency was confirmed also when the TTD versus PFS curves were compared. The median OS registered was 11.8 months. Patients with no liver metastases showed a longer median time of OS than patients with liver metastases. The mean value of RDI for the entire cohort was 87.4%.
Our study showed that TTD, calculated from the administration data is a useful proxy of TTF as registered in the clinical chart. TTD is a real-world outcome that can be used to demonstrate the efficacy of drugs used for administered therapies. It can be used as an end point for RWE studies, where the evaluation is less structured and standardized.
In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after ...the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue. Keywords: mRNA vaccine, COVID-19, Ph negative myeloproliferative neoplasms
Clinical studies based on novel rationales and mechanisms of action of chemotherapy agents and cytokines can contribute to the development of new concepts and strategies of antitumor combination ...therapies. In previous studies, we investigated the paradoxical immunostimulating effects of some chemotherapeutics and the immunoadjuvant activity of interferon alpha (IFN-α) in preclinical and clinical models, thus unraveling novel rationales and mechanisms of action of chemotherapy agents and cytokines for cancer immunotherapy. Here, we carried out a randomized, phase II clinical trial, in which we analyzed the relapse-free (RFS) and overall survival (OS) of 34 completely resected stage III-IV melanoma patients, treated with peptide-based vaccination (Melan-A/MART-1 and NY-ESO-1) in combination with IFN-α2b, with (arm 2) or without (arm 1) dacarbazine preconditioning. All patients were included in the intention-to-treat analysis. At a median follow-up of 4.5 years (interquartile range, 15.4-81.0 months), the rates of RFS were 52.9 and 35.3% in arms 1 and 2, respectively. The 4.5-year OS rates were 68.8% in arm 1 and 62.7% in arm 2. No significant differences were observed between the two arms for both RFS and OS. Interestingly, the RFS and OS curves remained stable starting from 18 and 42 months, respectively. Grade 3 adverse events occurred in 5.9% of patients, whereas grade 4 events were not observed. Both treatments induced a significant expansion of vaccine-specific CD8
T cells, with no correlation with the clinical outcome. However, treatment-induced increase of polyfunctionality and of interleukin 2 production by Melan-A-specific CD8
T cells and expansion/activation of natural killer cells correlated with RFS, being observed only in nonrelapsing patients. Despite the recent availability of different therapeutic options, low-cost, low-toxic therapies with long-lasting clinical effects are still needed in patients with high-risk resected stage III/IV melanoma. The combination of peptide vaccination with IFN-α2b showed a minimal toxicity profile and resulted in encouraging RFS and OS rates, justifying further evaluation in clinical trials, which may include the use of checkpoint inhibitors to further expand the antitumor immune response and the clinical outcome.
https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26.
Patients with cancer have an increased risk of complications from coronavirus disease 2019 (COVID-19) infection, including death, and thus, they were considered as high-priority subjects for COVID-19 ...vaccination. We report on the compliance with the COVID-19 vaccine of patients affected by solid tumours.
Patients with cancer afferent to Medical Oncology 1 Unit of Regina Elena National Cancer Institute in Rome were considered eligible for vaccination if they were receiving systemic immunosuppressive antitumor treatment or received it in the last 6 months or having an uncontrolled advanced disease. The Pfizer BNT162b2 vaccine was proposed to all candidates via phone or during a scheduled visit. The reasons for refusal were collected by administrating a 6-item multiple-choice questionnaire.
From 1st March to 20th March 2021, of 914 eligible patients, 102 refused vaccination (11.2%, 95% confidence interval CI 9.1–13.2). The most frequent (>10%) reasons reported were concerns about vaccine-related adverse events (48.1%), negative interaction with concomitant antitumor therapy (26.7%), and the fear of allergic reaction (10.7%). The refusal rate (RR) after 15th March (date of AstraZeneca-AZD1222 suspension) was more than doubled compared with the RR observed before (19.7% versus 8.6%, odds ratio OR 2.60, 95% CI 1.69–3.99; P < 0.0001). ECOG-PS 2 was associated with higher RR compared with ECOG-PS 0-1 (OR 2.94, 95% CI 1.04–8.34; P = 0.04). No statistically significant differences in RR according to other clinical characteristics were found.
Our experience represents the first worldwide report on the adherence of patients with cancer to COVID-19 vaccination and underlines how regulatory decisions and media news spreading could influence the success of the campaign.
•High mortality rate related to coronavirus disease 2019 (COVID-19) was observed in patients with cancer.•Cancer patients have high priority for COVID-19 vaccination for their vulnerability.•A refusal rate of 11.2% was found in our large cohort of eligible cancer patients.•Adequate information and clear regulatory decisions are required to promote vaccination.
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