COVID-19 patients with B-cell malignancies may deteriorate on bamlanivimab-etesevimab therapy

Reuters Health - 11/08/2021 - Co-treatment with bamlanivimab and etesevimab may induce SARS-CoV-2 immune-escape mutations and secondary clinical worsening in COVID-19 patients with B-cell malignancies, researchers from France caution in a new research letter.

Bamlanivimab and etesevimab are monoclonal antibodies that bind to SARS-CoV-2 spike receptor-binding domain, they explain in Annals of Oncology. Co-treatment has been shown to significantly reduce SARS-CoV-2 viral load at day 11 in patients with mild to moderate COVID-19.

In the BLAZE-1 trial, the drug duo cut the risk of COVID-related hospitalization or death by 70% compared with placebo. The finding led to a temporary use authorization for bamlanivimab and etesevimab in France to treat COVID-19 patients at high risk for severe disease.

In their letter, Dr. Fanny Pommeret with Gustave Roussy in Villejuif and colleagues describe 34 cancer patients (median age, 62.5 years) with mild-to-moderate SARS-CoV-2 infection who were treated with bamlanivimab (700 mg) plus etesevimab (1,400 mg) within five days of symptom onset.

Twenty-four patients had a solid tumor (71%) and 10 (29%) had hematological malignancies; 47% were receiving chemotherapy.

COVID-19 outcomes were "mostly favorable" with supplemental oxygenation required in only 29% of patients versus 41% in an historical (unpublished) cohort, the researchers report.

Two patients died from COVID-19 pneumonia. Both were later found to be infected by variants with the spike E484K mutation.

"Strikingly," say the researchers, all five patients (15%) with B-cell malignancies exhibited a worse clinical evolution, with delayed COVID-19 symptoms from day 14 to day 30 following bamlanivimab-etesevimab therapy. All of five had to be rehospitalized after day 14.

Viral-spike-gene sequencing on pre- and post-bitherapy nasopharyngeal swabs showed that four of the five B-cell cancer patients had acquired a mutation in the receptor-binding domain: three had a Q493R mutation and one had an E484D mutation.

Eli Lilly and Company, which sells the two drugs, declined to comment on the new report.

All five patients were rescued with convalescent plasma therapy: four patients recovered and were consequently discharged, and one died from COVID-19.

In their letter, Dr. Pommeret and colleagues note that patients with hematological malignancies are at high risk for developing severe COVID-19, "due to the inherent immune defect caused by the disease and therapy."

The current data suggest that this risk could be much higher in patients with hematologic B-cell malignancies, they add.

While bamlanivimab 700 mg plus etesevimab 1,400 mg is "effective in patients with solid tumors, patients with B cell malignancies present a secondary clinical deterioration associated with immune escape mutations," the researchers write.

"Our observation highlights the importance of clinical trials in this specific population, including comprehensive clinical and virological follow-up," they add.

Dr. Pommeret did not respond to a request for comment by press time.

SOURCE: https://bit.ly/3itHOyk Annals of Oncology, online August 2, 2021.

By Reuters Staff



Posted on 11 August 202124 August 2021