Haematological cancer: A risk factor for COVID-19?

A recent prospective study from the UK has suggested that among adult patients with cancer, those with haematological malignancies have an elevated risk of severe COVID-19.

The study population comprised 1,044 adults (median age 70 years, 56.9 percent male) with active cancer* and SARS-CoV-2 or COVID-19 enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP**) between March 18 and May 8, 2020. They were compared with a control population of adults with cancer based on 2017 data from the UK Office for National Statistics (non-COVID-19 group; n=282,878). Median follow-up in the UKCCMP cohort was 6 days, with patients followed up from time of COVID-19 diagnosis until hospital discharge or death. [Lancet Oncol 2020;doi:10.1016/S1470-2045(20)30442-3]

There was a higher proportion of men in the UKCCMP compared with the control cohort (56.9 percent vs 51.3 percent; odds ratio [OR], 1.26, 95 percent confidence interval [CI], 1.12–1.43; p=0.0002), though age did not significantly differ between cohorts.

Death occurred in 30.6 percent of the UKCCMP cohort (n=319), of which 92.5 percent (n=295) was attributed to COVID-19.

In patients with cancer and COVID-19, increasing age was associated with an increased risk of death (all-cause case fatality rate, 0.10 in patients aged 40–49 years and 0.48 in patients aged ≥80 years). Sex was also a factor predicting mortality, with a higher risk in men compared with women (35.6 percent vs 23.6 percent; OR, 1.92, 95 percent CI, 1.51–2.45; p<0.0001).

 

Is COVID-19 risk upped in haematological cancer patients?

A total of 227 patients in the UKCCMP cohort had haematological malignancies (leukaemia, myeloma, lymphoma).

Patients with haematological malignancies appeared to have a higher risk for COVID-19 compared with the control cohort. Compared with the control cohort, there was a higher prevalence of leukaemia (7.6 percent vs 2.8 percent; OR, 2.82, 95 percent CI, 2.21–3.55; p<0.0001), lymphoma (7.6 percent vs 4.8 percent; OR, 1.63, 95 percent CI, 1.28–2.06; p<0.0001), and myeloma (3.5 percent vs 1.8 percent; OR, 2.03, 95 percent CI, 1.42–2.83; p=0.0001) in the UKCCMP cohort.

Conversely, there were significantly fewer cases of breast (13.7 percent vs 16.3 percent; OR, 0.82, 95 percent CI, 0.68–0.98; p=0.026), prostate (10.9 percent vs 14.6 percent; OR, 0.72, 95 percent CI, 0.59–0.88; p=0.0008), and lung cancer (10.6 percent vs 13.7 percent; OR, 0.75, 95 percent CI, 0.61–0.91; p=0.0033) in the UKCCMP vs control cohort.

“Patients with haematological malignancies … are overrepresented, which is perhaps suggestive of an a priori increased susceptibility to viral infection,” proposed the researchers.

When compared with a control group of patients with digestive cancers, univariate analysis suggested a higher risk of mortality from COVID-19 among patients with prostate cancer, and a lower risk among patients with breast or female genital cancers compared with the rest of the UKCCMP cohort. These risks were no longer evident in the multivariate analysis. “[This highlights] the effect of patient age and sex on case-fatality rate,” noted the researchers.

COVID-19 trajectory was significantly more severe among patients with haematological cancers than those with solid organ tumours.

After adjusting for age and sex, patients with haematological cancers had a higher likelihood of requiring high-flow oxygen (OR, 1.82, 95 percent CI, 1.11–2.94; p=0.015), noninvasive ventilation (OR, 2.10, 95 percent CI, 1.14–3.76; p=0.014), admission to the intensive care unit for ventilation (OR, 2.73, 95 percent CI, 1.43–5.11; p=0.0019), and have severe or critical disease (OR, 1.57, 95 percent CI, 1.15–2.15; p=0.0043).

Patients with haematological cancers who had recently undergone chemotherapy (within 4 weeks of COVID-19 presentation) had an elevated mortality risk during COVID-19-related hospital admission (OR, 2.09, 95 percent CI, 1.09–4.08; p=0.028).

The case fatality rate was higher among patients with leukaemia compared with the rest of the UKCCMP population (OR, 2.25, 95 percent CI, 1.13–4.57; p=0.023).

 

Findings could lead to more focused management strategies

Patients with cancer have been identified as a population at risk of SARS-CoV-2 infection and more severe outcomes of COVID-19, said the researchers. “However, cancer encompasses many different diseases, with a diverse array of primary tumour subtypes and stages, affecting a heterogeneous group of patients of all ages, with very different prognoses and outcomes.”

This has led to new management strategies for all patients with cancer “including shortening of radiotherapy, switching from intravenous to oral chemotherapy regimens, and modifications in immunotherapy use,” they added.

“Our results show that patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 and differing COVID-19 disease phenotypes, with notable increased SARS-CoV-2 hospital presentations in patients with haematological cancers,” they said.

“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,” they continued.

“For the first time, we have a comprehensive analysis to determine who is more at risk of COVID-19. It is important to note that whilst cancer patients are more vulnerable, the chance of any given patient getting infected with COVID-19 remains low,” noted study first author Dr Lennard Lee, Academic Clinical Lecturer, University of Oxford, UK.

“Using these new data we are working fast to identify trends and correlations, which will enable us to create a tiered risk assessment tool so we can more precisely define the risk to a given cancer patient and move away from a blanket “vulnerable” policy for all cancer patients, in the event of a second wave of COVID-19,” added study senior researcher Professor Rachel Kerr, also from the University of Oxford.

As for the elevated mortality rate in leukaemia patients, immunological disruptions and “the use of intensely myelosuppressive treatment regimens” may increase their risk of initial SARS-CoV-2 infection and subsequent severity of disease, suggested the researchers. Identifying the causes of this finding is vital, they added, calling for further research.

The researchers noted that as the UKCCMP cohort comprised patients with metastatic cancer or currently undergoing treatment, the results may not apply to all patients with cancer. Additionally, the control cohort was not limited to patients with metastatic or active cancer.