COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study


People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.


This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.


The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both).


Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Author list


Lennard YW. Lee, (DPhil) 

Maria C. Ionescu, (MSC) 

Thomas Starkey, (MSci) 

Martin Little, (MRes) 

Michael Tilby, (MBChB) 

Arvind R. Tripathy, (MD) 

Hayley S. Mckenzie, (PhD) 

Youssra Al-Hajji

Nathan Appanna

Matthew Barnard, (PhD) 

Liza Benny, (PhD) 

Alexander Burnett, (FRCR) 

Emma L. Cattell, (PhD) 

James J. Clark, (MBBChir) 

Sam Khan, (PhD) 

Qamar Ghafoor, (MBChB) 

Hari Panneerselvam, (MBBS) 

George Illsley, (BSc) 

Catherine Harper-Wynne, (MD) 

Rosie J. Hattersley, (MBChB) 

Alvin JX. Lee, (PhD) 

Oliver Lomas, (DPhil) 

Justin KH. Liu, (MRCP) 

Amanda McCauley

NCRI Consumer Forum

Matthew Pang, (PhD) 

Jennifer S. Pascoe, (MRCP) 

James R. Platt, (MRes) 

Grisma Patel

Vijay Patel

Vanessa A. Potter, (PhD) 

Amelia Randle, (MRCP) 

Anne S. Rigg, (FRCP) 

Tim M. Robinson, (PhD) 

Tom W. Roques, (FRCR) 

René L. Roux, (MRCP) 

Stefan Rozmanowski, (MMath) 

Harriet Taylor

Mark H. Tuthill, (PhD) 

Isabella Watts, (BMBCh) 

Sarah Williams, (FRCP) 

Andrew Beggs, (FRCS) 

Tim Iveson, (MD) 

Siow Ming Lee, (FRCP) 

Gary Middleton, (FRCP) 

Mark Middleton, (PhD) 

Andrew Protheroe, (MD) 

Matthew W. Fittall, (PhD) 

Tom Fowler, (PhD) 

Prof Peter Johnson, (MD) 

on behalf of theUK Coronavirus Cancer Programme


Novel Coronavirus SARS-CoV-2


European Journal of Cancer