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Preprint looking at antibody immune response following one dose of Pfizer COVID-19 vaccine in cancer patients

Update

A preprint, an unpublished non-peer reviewed study, looks at the safety and immune-efficacy of 1 versus 2 doses of the Pfizer-BioNTech COVID-19 vaccine in cancer patients.

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March 11, 2021

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Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines

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This work has not been scrutinised by independent experts, or the story does not contain research data to review (for example an opinion piece). If you are reporting on research that has yet to go through peer-review (eg. conference abstracts and preprints) be aware that the findings can change during the peer review process
Peer-reviewed
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Expert Comments: 

Dr Peter English

This is a comment on a pre-print paper reporting interim results on the efficacy of the Pfizer-BioNTech vaccine (generic name BNT162b2) in cancer patients.1  This paper has already been reported in the media.2 eg

This paper describes an observational study, looking at blood samples from cancer patient who had received the vaccine.

Apart from commenting that the results are plausible, and may well be substantiated by further research, I will not go into many details of the scientific validity of the paper – others, including Evans and Armanath have already done so.3  I will, however, note that the “healthy controls” were “most[ly]… health care workers”.  As such, there may be substantial differences between the healthy controls and the cancer patients, other than their cancer status.

My comments below are on the implications, if this study’s findings are confirmed.

It looks like cancer patients may respond less well to a single dose of vaccine (although the very early reporting – before most have had time for the immune response to grow beyond 3 weeks – means that it might just take them longer than others to respond to the first dose).

The clear finding from this study (if confirmed) is that people with cancer are less likely to develop (or rather, to develop fewer) neutralising antibodies than healthy controls to the SARS-CoV-2 virus that causes Covid-19) after a single dose of vaccine.  This may apply even more to those with haematological cancers (although the number of such patients was small, so findings are less conclusive).  Similar findings applied to measures of the T-cell response, although this is more complex and the implications are even less clear.

Patients with solid tumours did, however, show a significant boosting effect, producing much higher antibody levels from two-weeks after boosting at three weeks.  (There were too few patients with haematological cancers to draw conclusions on this, for this group.)

This study initially gave the second dose at three weeks, but, when national policy changed after 29 December moved to planning to give the second (booster) dose at 12 weeks.

The study suggests that cancer patients may be less well protected by a single dose of vaccine than in healthy patients, at least in the initial three-week period after the first dose of vaccine.

We already know, however, that (generally) immunity continues to build at least for the first three weeks, and probably for considerably longer.  Will cancer patients immune response following a single dose continue to improve over time?  It is possible that antibody levels would cease climbing after three weeks in such patients (although I think this unlikely); or that they will plateau sooner or later than in healthy patients; or that they will plateau at the same or a lower level.

The results presented are interim, early findings.  More data will emerge over time, which will provide clearer answers to these questions.

Many patients received cancer treatment within weeks before or after vaccination.  The extent to which the effects on vaccine efficacy are a consequence of the original cancer, or of the treatments, is not entirely clear.

Interestingly – and in contrast to some other papers – this paper found lower neutralising antibodies to the B.1.1.7 variant after the first dose in healthy controls.

So what should professionals and patients make of this paper?

First, please don’t panic.  These are interim findings.  They are complex, and professionals will need to take some time to consider and discuss them.

It may be that cancer patients will have less protection in the first few weeks after vaccination than healthy people; but will be protected as well – or nearly as well – as others after a booster dose.  It is not clear whether the difference is sufficient to warrant bringing forward the booster dose, and giving it earlier than 12 weeks.

Indeed, as the efficacy of the booster dose – the quality and likely duration of the immune response it induces – increases with a longer prime-boost interval, the consequences of giving the second booster dose earlier might be a reduced longer-term immune response.

This, however, is likely to be overcome by a subsequent booster dose; and announcements that a booster dose (probably explicitly covering newer variants) is likely to be recommended for everybody may make this concern hypothetical.

It is possible that policy will be changed, with cancer patients being recommended to receive their [first] booster dose sooner than at 12 weeks; or, possibly, for example, to have their response to vaccination tested and an earlier booster recommended depending on their response – but we need to await clarification of any such changes.  Patients will be advised if they need to do anything – if the policy does change, patients will likely simply be invited for their second dose (or testing etc).  Similarly, we need to be patient and await further decisions about subsequent booster doses for this group, and for the wider population.

Many cancer patients be in the “clinically extremely vulnerable” group, included in vaccination priority group 4 (and who therefore should already have been offered their first dose of vaccine).4

For the time being, the advice for cancer patients should be, therefore, to arrange to have their first dose of vaccine if they haven’t already done so (assuming they are eligible), and to continue to follow shielding advice.5  The population-wide Covid-19 restrictions (the “lockdown”) will continue to provide them with considerable protection.  It may be appropriate to review and/or extend the shielding advice for these patients before it comes to an end at the end of March.

I would urge patients NOT to call their doctors for advice just yet.  It will take some days, at least, for decisions about whether to change policies based on these findings to be made and promulgated; calling before this has been done will simply overload the systems, and doctors may struggle to provide good advice.

Ideally, as suggested in the paper, household contacts of cancer patients should “shield by proxy” to reduce the chances that they will bring the infection into the household.  Cancer patients may be particularly vulnerable to a bad outcome if they get Covid-19.  This paper suggests they may also be less protected until 2 weeks after a booster dose of vaccine, so, if they are exposed to a suspected case, clinicians might wish to consider the use of prophylactic treatment e.g. with MABs.

This paper specifically considers vaccine efficacy in cancer patients.  The extent to which differences in cancer patients (compared to healthy people) is due to their underlying cancer, or to the treatment they are receiving.  Either way, it is possible that similar findings would apply to other patients who have immune or autoimmune conditions, or who are on immune suppressive treatment – patients with rheumatoid arthritis, for example.

Any speculation about driving mutation and variant strains is highly speculative, and this is not mentioned in the pre-print paper.  The main driver of variants is widespread transmission (and therefore replication) of the virus.  A possible, short-term increase in replication in cancer patients is unlikely to have a significant effect on the likelihood of new variants emerging in my opinion.

  1. Monin-Aldama L, Laing AG, Muñoz-Ruiz1 M, McKenzie1 DR, del Molino del Barrio I, Alaguthurai T, et al. Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines. Pre-print 2021.
  2. Roxby P. Cancer patients ‘lack same protection’ after first jab. BBC News 2021; Updated 11 Mar 2021; Accessed: 2021 (11 Mar (11:00 GMT)): (https://www.bbc.co.uk/news/health-56351084).
  3. Evans S, Amarnath S. Expert reaction to preprint looking at antibody immune response following one dose of Pfizer COVID-19 vaccine in cancer patients. Science Media Centre 2021; Updated 11 Mar 2021; Accessed: 2021 (11 Mar (10:30 GMT)): (https://www.sciencemediacentre.org/expert-reaction-to-preprint-looking-at-antibody-immune-response-following-one-dose-of-pfizer-covid-19-vaccine-in-cancer-patients/).
  4. Department of Health and Social Care. Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020. Independent report 2020; Updated 30 Dec 2020; Accessed: 2020 (30 Dec): (https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020/joint-committee-on-vaccination-and-immunisation-advice-on-priority-groups-for-covid-19-vaccination-30-december-2020 or via https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020).
  5. Department of Health and Social Care, Public Health England. Guidance on shielding and protecting people who are clinically extremely vulnerable from COVID-19. COVID-19: guidance on shielding and protecting people defined on medical grounds as extremely vulnerable 2020; Updated 25 Feb 2021; Accessed: 2021 (11 Mar): (https://www.gov.uk/government/publications/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19).

Prof Lawrence Young

This preprint shows that one dose of the Pfizer/BioNTech mRNA vaccine is ineffective at inducing a protective serological immune response in the majority of cancer patients.  Only 39% of those with solid cancers and 13% of those with blood cancer had an antibody response as compared to 97% of those without cancer.  A subsequent booster jab after 21 days was able to stimulate a robust immune response in 95% cancer patients.  The study raises concerns about delaying the booster jab for more than 21 days highlighting that the majority of vaccinated cancer patients will remain wholly or partially immunologically unprotected for at least 5 weeks after the primary vaccination.  The study is well-executed but has relatively few cancer patients, particularly in the blood cancer group.  We need more information on how cancer patients are responding to different vaccines.  Nevertheless this study does raise the issue of whether patients with cancer, other diseases or those undergoing therapies that affect the body’s immune response (e.g. transplant recipients, rheumatoid arthritis) should be fast-tracked for their second vaccine dose.

Prof Stephen Evans

It has been shown in a number of studies that those with haematological malignancies, and to a lesser degree those with other cancers, are at increased risk of death from Covid-19, especially relatively soon after their diagnosis.

This study examines such a group of vulnerable patients, all of whom have been given the Pfizer/BioNTech vaccine.  At points it is described as a trial but none of the relevant comparisons were randomised, so it is essentially an observational study, and inevitable limitations must therefore be taken into account.  The change in UK policy around delaying a second dose of vaccine allowed for the authors to make some comparisons between those who received a second dose within 21 days and those who did not.  They have not yet provided data on those who received a second dose after a 12 week delay.

It has used blood tests to evaluate the immune response to the Covid-19 vaccine, and although it refers to “efficacy” it is not the same as the clinically-based “Vaccine Efficacy” measured in the large randomised trials, so the percentages quoted should not be compared with those from the large trials which have been headline figures in the media.

Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer.  Sadly, it would appear that two patients who were positive for Covid-19 died before 21 days, presumably prior to their getting a second dose of vaccine.  It does not seem to be commented on but from one of the figures a third patient died about 34 days after their first dose, but it is not clear whether they received a second dose of vaccine.  The authors also note that no patients, whether they had a second dose at 21 days or not, had a positive test for Covid after 21 days, but they argue that this does not affect their view that the second dose must be given within 21 days (for the Pfizer vaccine).

The authors make it clear that the general advice about other measures to be taken for protection are still relevant – stating it is “important that this population continues to observe all COVID-19-associated measures such as social distancing and shielding when attending hospitals, even after vaccination”.

These data will undoubtedly need to be examined by JCVI, but the evidence that harm has been caused to patients with cancer by delaying a second dose has not yet been demonstrated conclusively.  Full follow-up of those who get vaccinated with a delayed second dose will be very important.

Dr Shoba Amarnath

Is this robust science; what are the strengths and limitations of the study?

This study is of immediate importance to patients with solid cancers with respect to COVID-19 vaccine delivery.

What does the data show – is it convincing?

The study determined the effect of single and multiple doses of COVID-19 vaccine in cancer patients at five week period.  They show that in healthy controls 97% of people have a robust immune response at five weeks after a single dose of vaccine.  By contrast less than half of patients with solid cancers have an immune response.  This immune response is impressively increased (95%)  to similar levels as healthy controls with a second dose of vaccine at day 21.  They conclude that patients with solid cancers need two doses of vaccine in a timely manner to prevent the possibility of infection during this time.

How does it fit with what we know from other data?

The findings presented here is the first report on safety and immunological efficacy of COVID-19 vaccine in patients with solid cancers.

Do we know why there might be a different immune response in people with cancer than people without cancer?

All of these findings are consistent with our understanding of the immune system function in cancer patients.  We know that the immune system within cancer patients is compromised as compared to healthy controls.  Hence, a 2nd vaccine boost prepares the dysregulated immune system to function at the same efficiency as healthy controls.

Do the numbers suggest more people would get some protection if more first doses are given, than if fewer people get both doses, or not?

The data in the study supports the notion that in solid cancer patients a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.  It does not draw any conclusions on the best use of the vaccine in healthy members of the public.

Any other comments about this data?

The study was unable to compare the effectiveness of a second dose of vaccine at day 21 with that given after 12 weeks to see if there are any long-term advantages or disadvantages with respect to immune system function in case of a delayed second vaccine challenge.

Q&A

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