Patients with chronic lymphocytic leukemia (CLL) and COVID-19 have a higher risk of death if they have received CLL treatment, according to a retrospective analysis published in Leukemia.1

Prior studies produced conflicting results regarding the impact of CLL treatment on COVID-19 outcomes. In one study, patients with recent or ongoing CLL treatment were more likely to have milder COVID-19, and patients who received ibrutinib were less likely to be hospitalized.2 In another study, there was no difference in COVID-19 severity or mortality between patients who received CLL treatment and those who did not.3

With the current study, researchers assessed factors associated with COVID-19 outcomes in a cohort of 941 patients with CLL and confirmed COVID-19. There were 887 patients diagnosed with CLL, 38 with small lymphocytic lymphoma, and 16 with monoclonal B-cell lymphocytosis.

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There were 547 patients who had received at least 1 line of CLL treatment, 320 patients who were on treatment at the time of SARS-CoV-2 infection, and 394 patients who had never received treatment for CLL.

For patients on treatment at the time of infection, treatment types included BTK inhibitor monotherapy (56.3%), venetoclax monotherapy (10.7%), and chemoimmunotherapy (9.1%).

About three-quarters of patients (74.7%) were hospitalized with COVID-19, 25.5% were admitted to the ICU, and 27.3% died. About two-thirds of patients who were receiving CLL treatment at the time of infection stopped treatment (66.2%).

CLL treatment was not associated with COVID-19 severity. The factors associated with severity in a multivariate analysis were age (odds ratio [OR], 1.04; 95% CI, 1.02–1.06; P <.001), hypogammaglobulinemia (OR, 1.69; 95% CI, 1.20–2.38; P =.002), and coronary artery disease (OR, 2.83; 95% CI, 1.37–6.61; P =.009)

However, CLL treatment was associated with mortality in a multivariate analysis. The risk of death was lower in patients who had not received any CLL treatment (hazard ratio [HR], 0.54; 95% CI, 0.41-0.72; P <.001) compared with patients who had received treatment.

There were no significant differences by treatment type, but treated patients in any category had worse overall survival when compared with untreated patients (P <.001).

The multivariate analysis also suggested the risk of death was higher for older patients (HR, 1.03; 95% CI, 1.02-1.04; P <.001) and for those with cardiac failure (HR, 1.79; 95% CI, 1.04-3.07; P =.035).

“Taken together, our findings suggest that, in patients with CLL and COVID-19, older age confers a worse prognosis, with increased mortality,” the researchers wrote. “Untreated patients had a better chance of survival than those on treatment or recently treated.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Chatzikonstantinou T, Kapetanakis A, Scarfò L, et al. COVID-19 severity and mortality in patients with CLL: An update of the international ERIC and Campus CLL study. Leukemia. Published online November 1, 2021. doi:10.1038/s41375-021-01450-8
  2. Scarfò L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: A joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020;34(9):2354-2363. doi:10.1038/s41375-020-0959-x
  3. Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in patients with CLL: A multicenter international experience. Blood. 2020;136(10):1134-1143. doi:10.1182/blood.2020006965