BackgroundThe efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 MESHD
(SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer MESHD
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 MESHD
, 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 MESHD
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 MESHD
patients was strikingly low (below 40%) and very low in haematological cancer MESHD
patients (below 15%). Of note, efficacy in solid cancer MESHD
patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer MESHD
patients were boosted for clear conclusions to be drawn.
ConclusionsDelayed boosting potentially leaves most solid and haematological cancer MESHD
patients wholly or partially unprotected, with implications for their own health; their environment and the evolution of VOC strains. Prompt boosting of solid cancer MESHD
patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer MESHD
RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSSome cancer MESHD
patients have been shown to exhibit sustained immune dysregulation MESHD
, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD
. 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 MESHD
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 MESHD
patients and those on systemic anti- cancer MESHD
Added value of this studyWe report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer MESHD
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 MESHD
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 MESHD
exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer MESHD
patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers MESHD
, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ring vaccination, and careful follow-up should be prioritised.