Findings from a UK study published in The Lancet Oncology indicate that cancer patients with different tumour types have variable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and coronavirus disease 2019 (COVID-19) phenotypes. In particular, patients with haematological cancers (leukaemia, lymphoma, or myeloma) had increased susceptibility to the virus, and were at greater risk of experiencing a more severe course of COVID-19 disease and requiring more intensive clinical support.
“Labelling all patients with cancer as susceptible to COVID-19 is probably neither reasonable nor informative,” according to Lennard Y W Lee, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK, and colleagues. “We report the first analysis, to our knowledge, of the complex interaction between patient demographics and tumour subtype, to more accurately estimate the risk of SARS-CoV-2 infection and COVID-19 in patients with cancer.”
Researchers compared adults with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (ONS, 2017 data). The primary outcome was the effect of primary tumour subtype, age, and sex and on SARS-CoV-2 prevalence and the case–fatality rate during hospital admission.
The authors report that 319 (30.6%) of 1044 patients in the UKCCMP cohort died, 295 (92.5%) of whom had a cause of death recorded as being due to COVID-19. The all-cause case–fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0.10 in patients aged 40–49 years to 0.48 in those aged 80 years and older.
Researchers noted that some tumour subtypes, such as haematological cancers, were overrepresented in the UKCCMP cohort compared with the ONS control population. Patients with haematological malignancies appeared to be at significantly increased risk of COVID-19 infection, including those with leukaemia (odds ratio [OR] 2.82, 95% CI 2.21–3.55; p<0.0001), myeloma (OR 2.03, CI 1.42–2.83; p=0.0001), and lymphoma (OR 1.63, CI 1.28–2.06; p<0.0001), “suggestive of an a priori increased susceptibility to viral infection.”
Cases of extranodal natural killer/T-cell lymphoma, Waldenström macroglobulinaemia, and unspecified neoplasm of lymphoid, haematopoietic and related tissue were greatly overrepresented, but “the reasons for this are unclear because of the small number of patients involved and stochastic effects,” the authors said. By contrast, patients with lung cancer and prostate cancer were relatively under-represented in the UKCCMP compared with the ONS controls.
Case–fatality rates for each primary tumour subtype in the UKCCMP were compared to a reference group – non-colorectal cancers of digestive organs – which had the median fatality rate. Univariable analysis showed a significantly higher risk of death from COVID-19 in patients with prostate cancer (OR 2.14, 95% CI 1.17–3.96; p=0·014) and leukaemia (OR 2.03, CI 1.04–3.97; p=0.038), and a significantly lower risk of death from COVID-19 for those with breast cancer (OR 0.53, CI 0.28–1.00; p=0.049) and female genital cancers (OR 0.36, CI 0.13–0.87; p=0.031). Following a multivariable correction for age and sex, patients with leukaemia still had a significantly higher risk of COVID-19-related death (OR 2.25, CI 1.13–4.57; p=0.023), compared with the rest of the UKCCMP cohort.
The authors also performed an analysis of 227 patients with haematological malignancies who were diagnosed with COVID-19, and compared them to the rest of the UKCCMP cohort of 817 patients with non-haematological cancers. After adjusting for age and sex, patients with haematological malignancies were significantly more likely to require high flow oxygen (OR 1.82, 95% CI 1.11–2.94; p=0.015), non-invasive ventilation (OR 2.10, CI 1.14–3.76; p=0.014), intensive care unit admission for ventilation (OR 2.73, CI 1.43–5.11; p=0.0019), and have a severe or critical disease course (OR 1.57, CI 1.15–2.15; p=0.0043).
In addition, 108 (47.6%) of 227 patients with haematological malignancies had received recent chemotherapy within 4 weeks of COVID-19 presentation, compared with 241 (29.5%) of 817 patients with non-haematological malignancies. Univariable analyses did not show any difference in mortality rate between recent use of chemotherapy and no recent chemotherapy. However, after correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2.09, 95% CI 1.09–4.08; p=0.028).
“Immunological disruption observed in patients with leukaemia and the use of intensely myelosuppressive treatment regimens might result in a combination of risks, in terms of the likelihood of initial SARS-CoV-2 infection, its ability to gain a foothold in the host, and in terms of the downstream disease course and likelihood of severe consequences, such as cytokine storm and multi-organ failure,” the authors explained.
The researchers also noted a low admission rate of patients with cancer to the intensive care unit, which could affect COVID-19 outcomes, and suggested this could be due to perceived futility of intensive support in patients with cancer and that it “[warrants] further investigation.”
“Our study is unique in comparing a large COVID-19 population with cancer to an accurate and geographically appropriate cancer population control dataset. Morbidity and case–fatality rates from COVID-19 in UK patients with cancer who attend hospital are relatively high, particularly in older patients and those with haematological malignancies, but not all cancer patients are affected equally. This important finding could allow clinicians some ability to risk stratify their patients and make informed decisions on appropriate levels of social isolation and shielding. Future work by the UKCCMP, in collaboration with international consortia, will define risk in much greater granularity, including different subtypes of a given tumour,” the authors said.