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BackgroundThe efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer diagnosis were hitherto excluded from trials of the vaccines currently in clinical use. MethodsThis study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose. FindingsThe vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls (>90% efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn. ConclusionsDelayed boosting potentially leaves most solid and haematological cancer patients wholly or partially unprotected, with implications for their own health; their environment and the evolution of VOC strains. Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSSome cancer patients have been shown to exhibit sustained immune dysregulation, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UKs dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer patients and those on systemic anti-cancer therapies. Added value of this studyWe report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population. Implications of all the available evidenceIn cancer patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ring vaccination, and careful follow-up should be prioritised.
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BackgroundThere is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. MethodsWe used data from a single large UK Cancer Centre to assess demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February-12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with severe disease. Initial diagnosis of cancer >24m before COVID-19 (OR:1.74 (95%CI: 0.71-4.26)), presenting with fever (6.21 (1.76-21.99)), dyspnoea (2.60 (1.00-6.76)), gastro-intestinal symptoms (7.38 (2.71-20.16)), or higher levels of CRP (9.43 (0.73-121.12)) were linked with greater COVID-19 severity. During median follow-up of 47d, 34 patients had died of COVID-19 (22%). Asian ethnicity (3.73 (1.28-10.91), palliative treatment (5.74 (1.15-28.79), initial diagnosis of cancer >24m before (2.14 (1.04-4.44), dyspnoea (4.94 (1.99-12.25), and increased CRP levels (10.35 (1.0552.21)) were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin (0.04 (0.01-0.04). ConclusionsA longer-established diagnosis of cancer was associated with increasing severity of infection as well as COVID-19 death, possibly reflecting effects of more advanced malignant disease impact on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients. Contribution to the fieldIn the context of cancer, the COVID-19 pandemic has led to challenging decision-making. These are supported by limited evidence with small case studies being reported from China, Italy, New York and a recent consortium of 900 patients from over 85 hospitals in the USA, Canada, and Spain. As a result of their limited sample sizes, most studies were not able to distinguish between the effects of age, cancer, and other comorbidities on COVID-19 outcomes. Moreover, the case series from New York analysed which patient characteristics are associated with COVID-19 death, but only made a comparison with non-cancer patients. The first results of the COVID-19 and Cancer Consortium provide insights from a large cohort in terms of COVID-19 mortality, though a wide variety of institutions with different COVID-19 testing procedures were included. Given the current lack of (inter)national guidance for cancer patients in the context of COVID-19, we believe that our large cancer centre can provide an important contribution to the urgent need for further insight into the intersection between COVID-19 and cancer. With comprehensive in-house patient details, consistent inclusion criteria and up-to-date cancer and COVID-19 outcomes, we are in position to provide rapid analytical information to the oncological community.