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Patients with B-cell non-Hodgkin lymphoma who are hospitalized for COVID-19 are at high risk of developing prolonged COVID-19. In a new study, nearly a third of more than 100 patients developed disease of longer course and were at increased risk for death.
“We can see that patients with B-cell non-Hodgkin lymphoma with COVID-19 have a high incidence of prolonged length of stay for SARS-CoV-2 infection,” said Caroline Besson, MD, PhD, of the Centre Hospitalier de Versailles, Le Chesnay, Université Versailles Saint-Quentin en Yvelines, France, in presenting the findings as part of the European Hematology Association (EHA) 2021 Annual Meeting.
“There is a need for guidelines for the management of lymphoma patients during the COVID-19 pandemic, especially concerning B-cell depletion and maintenance anti-CD20 [therapy],” she said.
Persistent SARS-CoV-2 infection, sometimes referred to as “long COVID,” is emerging as a concerning clinical syndrome among certain patient groups, including patients who are immunocompromised.
Patients with lymphoma who are treated with B-cell-depleting immunotherapy may be especially vulnerable, owing to an impaired immune response and potential development of B-cell aplasia, Besson noted.
The findings shed important light on the issue of prolonged COVID-19, said John Charles Riches, PhD, a clinical senior lecturer and honorary consultant oncologist at the Center for Haemato-Oncology, Barts Cancer Institute, London, United Kingdom, who was asked for comment.
“I think these findings are significant,” he told Medscape Medical News. “There have been a few case reports of anti-CD20 treatment being associated with prolonged COVID, but no large study such as this,” he noted.
Hospital Stays More Than 30 Days
To assess the incidence and outcomes of the prolonged COVID-19 syndrome among patients with lymphoma, Besson and her colleagues evaluated data on 111 adult patients with lymphoma who were admitted to 16 hospitals in France with COVID-19 in March and April 2020.
For the study, persistent COVID-19 was defined as having ongoing, severe symptoms of COVID-19 that required a hospital stay for more than 30 days or that required repeated hospitalization for COVID-19 after initial improvement, resulting in a total in-hospital length of stay of more than 30 days altogether.
Of the 111 patients, 24 died within 30 days of admission; 55 recovered from COVID-19 and were discharged from the hospital.
Thirty-one patients remained hospitalized after 30 days, and one patient was re-hospitalized for COVID-19 recurrence. The incidence of persistent COVID-19 was 29% (32 of 111).
“In context, the median length of in-hospital stay for COVID-19 is reported to be 5 to 20 days worldwide, depending on the requirement of intensive care,” Besson told Medscape Medical News. “The average stay was 11 days globally for patients hospitalized between March 1 and June 15, 2020.”
With a median follow-up of 191 days in the study, the overall survival rate at 6 months for the full cohort was 69%. Nine patients died after persistent COVID-19 (27%).
Among those with prolonged COVID-19, the median length of stay was 58 days, and the median duration of COVID-19 symptoms was 83 days. The median age of these patients was 64 years (range, 43 – 87 days); 63% were men.
Among patients with prolonged COVID-19, 69% had at least one significant comorbidity, compared with 58% of those without prolonged COVID-19.
In a multivariate analysis, factors associated with prolonged hospitalization with COVID-19 were older age (70 years or older; hazard ratio [HR], 2.34; P = .004); relapsed or refractory lymphoma (HR, 3.12; P = .028); treatment with anti-CD20 monoclonal antibody therapy within 12 months (HR, 2.26; P < .001); and having one or more comorbidities (HR, 1.50; P = .109).
The same factors were also significantly associated with a decreased risk of overall survival, with the risk exceptionally higher with age 70 years or older (HR, 4.73; P < .001). Risk was also higher with regard to relapsed/refractory lymphoma (HR 3.34; P = .002), anti-CD20 therapy (HR 2.17; P = .039), and having one or more comorbidities (HR, 2.50; P trend = .064).
Although 57% of the patients in the study overall had received B-cell-depleting therapy in the previous 12 months, the rate was 81% among those with prolonged COVID-19, vs just 40% of those without prolonged COVID-19.
Importantly, none of the patients who had T-cell lymphoma (n = 8) or classical Hodgkin’s disease (n = 8) experienced prolonged COVID-19.
“Indeed, this is another strong argument that B-cell depletion is a major risk factor for prolonged hospitalization for COVID-19,” Besson said.
A key underlying mechanism of the risk among those patients could be “dysfunctional immunological memory [which] may impair protection against reinfection and an anti-SARS-CoV-2 vaccine response,” Besson said.
“This should be further explored,” she said.
Obesity Not Implicated
A surprising finding of the study was in regard to obesity. It had been established that obesity is a leading risk factor for COVID-19 severity, and it was recently described as increasing the risk for prolonged COVID-19, yet obesity did not appear to increase the risk in the current study, Besson noted.
“Obesity, hypogammaglobulinemia, or lymphopenia are not significantly associated with a worse outcome,” she explained.
“Concerning obesity, this is probably due to the fact that patients with relapsed/refractory lymphoma frequently lose weight,” she said.
She added that with regard to hypogammaglobulinemia or lymphopenia, “we may lack power to have significant associations with these factors.”
Balancing Lymphoma Treatment Benefits With COVID Risks
In terms of addressing the higher risk with anti-CD20 therapy without compromising patients’ lymphoma therapy, Besson noted that “this is the most difficult point.
“In the context of a surge of COVID-19 cases, it may be safer to hold on maintenance with B-cell depletion in patients in complete remission of their lymphoma,” she said.
“In any case, patients receiving these therapies should be given extra education on how to prevent the infection, and their proxies and medical teams should be vaccinated,” she said.
Choices Are Not Easy
The UK’s Riches also pointed out that “it makes sense that depleting the humoral immune system will have an effect on COVID-19 patients with some types of B-cell lymphoma also have an immune defect associated with the lymphoma.”
He continued: “In addition, the flip side is that several studies have shown some benefit for convalescent plasma, also suggesting that antibodies are important.”
Riches agreed that the choices are not easy when it comes to addressing concerns of the anti-CD20 therapy risk.
“It would be sensible to avoid anti-CD20 therapy when COVID-19 rates are high and the benefit of the anti-CD20 therapy is marginal, [for instance] with maintenance rituximab for follicular lymphoma,” Riches said.
Besson and Riches have disclosed no relevant financial relationships.
European Hematology Association (EHA) 2021 Annual Meeting: Abstract S215. Presented June 11, 2021.
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