Patients with cancer typically number among the most vulnerable people during an infectious disease outbreak, and early reports from China during the current coronavirus pandemic appeared to support that concern with coronavirus disease 2019 (COVID-19).1 But “patients with cancer” are not homogenous: they comprise a diverse range of different types of cancers, different therapies, different stages of recovery or palliative care and different demographics. As researchers seek to learn more about the SARS-CoV-2 infection, emerging studies are beginning to look at the risks and outcomes associated with COVID-19 among people with specific cancer types.

Though very small, a new interim report of a case series in Barcelona suggests that patients with chronic lymphocytic leukemia (CLL) may not follow as severe a course of COVID-19 as might be expected, given the susceptibility of patients with blood cancers to respiratory infections and the immunodeficiency that often accompanies CLL.2 Rather, the very immunodeficiency that suggests these patients would be at higher risk for severe illness and death — and possibly the immune-suppressing therapeutic agents that treat CLL — may actually be a protective factor if future studies lead to findings similar to those currently being reported.

“If it is eventually confirmed that CLL does not necessarily facilitate COVID-19 infection and is not a risk factor for severe infection, particularly pneumonia, this will be extremely important for CLL patients and CLL referral centers,” senior author Emili Montserrat, MD, PhD, an emeritus professor of medicine at the University of Barcelona Hospital Clinic and Director of Hemato-Oncology at the Clinica Teknon, told Cancer Therapy Advisor.

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But Dr Montserrat stressed that the findings require considerable caution because they rely on just 4 patients at a single center in Barcelona and may not include all the patients at that center who became infected with COVID-19.

“The main reason we carried out this exploratory analysis was that when the COVID-19 pandemic arrived in Spain, we received many calls from our patients and colleagues to inquire about the likelihood that CLL patients contract COVID-19, and its likely severity,” Dr Montserrat said. “When the COVID-19 outbreak arrived at its peak we decided to look at our data.”

An estimated 4.2 per 100,000 people in Western countries receive a CLL diagnosis each year, an incidence that jumps to 30 people per 100,000 among those over age 80 years. In the United States, that adds up to more than 20,000 new cases of CLL in 2019, according to National Cancer Institute Surveillance, Epidemiology, and End Results Program.3

All 4 Patients Had Good Outcomes

The study involved patients with CLL registered at The Hospital Clinic in Barcelona and was conducted from 2000 to 2019. The researchers included 804 patients with a median age of 67 years and a median overall survival of 11.8 years. The authors noted that of those who died and had information on cause of death available, just over a third (35%) died from infection (236 patients). Infection is a leading cause of death among patients with CLL, the authors noted, and many people with CLL tick off 3 or 4 boxes for COVID-19 risk factors for poor outcomes, including cancer, older age, immunodeficiency, and, often, chronic comorbidities.

Of the 420 patients currently registered at the clinic, 4 of them (0.95%) were diagnosed with COVID-19. The authors described the demographics and clinical course for these 4 patients, all of whom were male and all of whom experienced mild infections that never required intensive care. Three of the patients “had increased ferritin levels; 2 presented with lymphocytopenia; and 1 had increased D-dimer levels, all features associated with poor outcome in COVID- 19,” the authors noted. Two patients had received CLL therapy previously.

However, 3 of the patients recovered within 4 to 8 days, and the fourth patient recovered 24 days later following an experimental therapy.

Dr Montserrat emphasized that their data are preliminary and that some CLL patients with COVID-19 may not have been identified or received treatment elsewhere, necessitating longer follow-up and validation from other research. “I am aware that in other CLL series, the data do not look as promising as in ours,” he told Cancer Therapy Advisor.

Stephen E.F. Spurgeon, MD, an associate professor of medicine and section chief of Hematologic Malignancies at Oregon Health & Science University’s Knight Cancer Institute in Portland, said the findings in this small study both are and are not surprising. The outcomes of these patients lend some cautious optimism, but “I don’t think we would have been surprised if they had 0 or 4 survivors in that series,” he told Cancer Therapy Advisor. Though the paper is hypothesis generating, it highlights the need for COVID-19-related studies with large cohorts of CLL patients.

“What I tell my patients in the world of CLL is that not all CLL is created equal,” Dr Spurgeon said. “You have to understand what prior therapy patients have had, are they patients with active disease, progressive disease, are they on ibrutinib, are they on observation? All those things could influence the outcome, and it’s going to take these large databases to understand.”

Kerry A. Rogers, MD, an assistant professor of hematology at The Ohio State University’s Comprehensive Cancer Center in Columbus, agreed that the findings are both surprising and unsurprising, particularly given how few patients are involved.

“We assume CLL patients would be at risk for death or severe COVID-19 disease because everyone with CLL lives at a higher risk for infections” and has weaker immune systems particularly when it comes to respiratory infections, Dr Rogers told Cancer Therapy Advisor. But she agrees the study can only be hypothesis generating, definitely not practice changing.

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“This is not going to make me tell my patients to do anything differently, but it is really encouraging just to see that people with CLL survived this, and 4 of them did well,” she said.

Both Dr Rogers and Dr Spurgeon said the prevalence cited at the center, just under 1%, was not informative, because the center could not confirm infection status for every patient. “They also don’t take into account or state what the prevalence of COVID-19 disease is in their general population in that area,” or what measures patients are taking to protect themselves, Dr Rogers added.

“You’d have to call all 420 patients and find out, ‘Did you stay home? Are you going [out to get] groceries? Have you had a household with COVID or go to work with someone that had COVID?’” she explained. Most of her patients are terrified of the disease and have not left their home in 3 months.