Close Monitoring Recommended Despite Reduced Risk of COVID-19 Mortality in CLL

Carsten Niemann, MD, PhD

Although lower fatality rates were reported during the omicron wave of the COVID-19 pandemic in patients with chronic lymphocytic leukemia (CLL), close monitoring and preemptive antiviral therapy is still recommended following a positive SARS-CoV-2 test, particularly in patients with close hospital contacts and those older than 70 years of age with at least one comorbidity, according to data from a study published in Blood.¹

The findings showed that the rates of hospitalizations and intensive care unit (ICU) admissions declined significantly, but the 30-day mortality rate reached 23% during the height of the omicron sublineage BA.2 variant. However, for a larger population-based cohort of patients with CLL, including the hospital cohort, the 30-day mortality rate was 2%.

“The omicron variant is reported to give milder disease in the general population; outcomes for immunocompromised patients have not been reported,” lead study author Carsten Niemann, MD, PhD, clinical associate professor and principal investigator at Rigshospitalet in Copenhagen, Denmark, and coauthors, wrote in the publication. “Here, hospital‐ and population‐based data on outcome[s] in CLL upon infection with the omicron variant of SARS‐CoV‐2 warrants close monitoring and preemptive therapy upon a positive SARS‐CoV‐2 test for patients with CLL and frequent hospital contacts; other patients with CLL can expect a mild course of COVID‐19.”

Prior data have shown high mortality rates in patients with CLL who have been diagnosed with COVID-19. Although a milder disease course with the omicron variant has been reported in the general population, the outcome in immunocompromised patients is not well known.

As such, investigators evaluated the time to hospitalization and admission to the ICU, and 30-day mortality following infection with SARS‐CoV‐2 in a cohort of Danish patients with CLL with a SARS‐CoV‐2 polymerase chain reaction (PCR) test from electronic health records (EHR) between March 2020 through January 2022 (EHR cohort).

Additionally, investigators examined a population cohort comprised of patients registered with a diagnosis of CLL in the Danish CLL registry for whom a positive SARS‐CoV‐2 PCR test was identified through the PERSIMUNE treatment database.

Because data on variants were not available for most patients, investigators grouped patients into four time periods based on their first positive SARS‐CoV‐2 test: March 2020 through December 2020 (period 1); January 1, 2021, through November 25, 2021 (period 2); November 26, 2021, through December 31, 2021 (period 3); and January 1, 2022, through January 28, 2022 (period 4).

Until January 28, 2022, 151 patients in the EHR cohort had 153 cases of COVID‐19 that had been confirmed with a positive PCR test. Additionally, 640 patients in the population cohort had a positive PCR test.

A total of 59, 40, 32, and 22 patients in the EHR cohort had a positive PCR test in time periods 1, 2, 3, and 4, respectively. In the population cohort, 24, 66, 73, and 477 patients had a positive PCR test in periods 1, 2, 3, and 4, respectively.

No significant differences in baseline characteristics were reported between the four periods. However, patients in the EHR cohort were significantly older vs those in the population cohort (P = .0052); those in the EHR cohort were also diagnosed with CLL significantly more recently than those in the population cohort (P = .024). Similar rates of patients in the EHR and population cohorts had received therapy for CLL before testing positive for COVID-19, at 39% (n = 43/109) and 30% (n = 190/640), respectively (P = .054).

Additional findings showed that in the EHR cohort, the rate of hospitalizations for patients with COVID-19 was more than 75% higher during the second period vs periods 3 and 4 when omicron emerged and peaked, respectively, and where preemptive monoclonal antibodies were administered to hospitalized patients (P < .014). During periods 3 and 4, monoclonal antibodies were also administered at outpatient visits, reflecting 30-day admission rates of between 56% and 60% vs 83% during period 2.

ICU admission rates peaked before the onset of omnicron, at between 12% and 12.5% vs between 0% and 3% in the prior period.

In the EHR cohort, the 30‐day overall survival (OS) rate ranged from 77% to 91% across all four periods, comparing favorably to the between 64% and 73% OS rate reported in the first part of the pandemic.

Regarding variant types, 5 out of the 6 patients who died in period 3 had the delta variant.

The 5 patients who died within 30 days of a positive PCR test in period 4 were older than 71 years and all had comorbidities, including dementia, other malignant diseases, diabetes, and cardiac and pulmonary comorbidities. Four of these 5 cases had the omicron variant; variant data were missing for the last case. Three of these 5 patients died from respiratory failure, and 2 died at home without a known cause of death. Treatments included monoclonal antibodies and dexamethasone (n = 2) and remdesivir (n = 1); the 3 other fatal cases did not receive COVID-19–specific therapy.

Notably, 30‐day survival rates rose from periods 2 through 4 in the population cohort from 93.9% to 94.5% and 99.2%, respectively; no deaths were reported in period 1, during which time mass testing started (P < .002). Across both the EHR and population cohorts, the 30‐day OS rates rose from periods 1 through 4 from 88.0% to 89.6%, 93.3% and 98.2%, respectively, with a significantly higher OS in the omicron BA.2 period vs periods 1 through 3 (P ≤ .0077).

Reference

1. Niemann CU, Cunha-Bang CD, Helleberg M, et al. Patients with CLL have lower risk of death from COVID-19 in the omicron era. Blood. Published online May 19, 2022. doi:10.1182/blood.2022016147