Prolonged COVID-19 Is Common Among Patients with Lymphoma

COVID-19 leads to hospitalization in B-cell non-Hodgkin lymphoma patients, who are at high risk of developing prolonged COVID-19. A new study reported that approximately one-third of more than 100 patients developed longer-lasting COVID-19 and that these patients had a higher risk of death.

Prolonged COVID-19 with B-cell depletion

Dr. Caroline Besson of France said while presenting the findings as part of the European Hematology Association (EHA) 2021 Annual Meeting: "We can see that SARS-CoV-2 infection lasts a long time in patients with B-cell non-Hodgkin lymphoma who have COVID-19. Guidelines are needed for managing lymphoma patients during the COVID-19 pandemic, particularly regarding B-cell depletion and anti-CD20 protection (treatment)."

Sometimes called "long COVID", persistent SARS-CoV-2 infection is emerging as a concerning clinical syndrome in certain groups of patients, including those who are immunocompromised. Besson reported that lymphoma patients receiving B-cell-depleting treatments may be particularly vulnerable because of an impaired immune response and the potential development of B-cell aplasia.

Oncologist Lohn Charles Riches of Barts Cancer Institute in London, United Kingdom, said the findings shed important light on prolonged COVID-19. “I think these findings are important. There have been a few case reports of anti-CD20 treatment (for example, rituximab) associated with long COVID, but no study like this.”

More than 30 days in hospital

To assess the frequency and outcomes of prolonged COVID-19 syndrome in lymphoma patients, Besson and colleagues examined data on patients presenting to 16 hospitals in France with COVID-19 in March and April 2020, including 111 adult lymphoma patients whose records were evaluated.

In the study, persistent COVID-19 was defined for people requiring more than 30 days in hospital or repeated hospitalization for COVID-19 after initial recovery.

Of the 111 patients, 24 died within 30 days of admission; 55 recovered and were discharged. 31 patients remained in hospital for more than 30 days, and one patient was hospitalized again because of recurrent COVID-19. The frequency of persistent COVID-19 was 29% (32 of 111).

Besson said: “The average length of hospital stay for COVID-19 is reported to be 5 to 20 days worldwide, depending on the need for intensive care. For patients hospitalized between March 1 and June 15, 2020, the average length of stay worldwide was 11 days".

With a median follow-up of 191 days, the 6-month overall survival rate for the entire group was 69%. 9 patients died after persistent COVID-19 (27%).

Those who developed prolonged COVID-19 had an average hospital stay of 58 days and a median duration of COVID-19 symptoms of 83 days. These patients had a median age of 64 (range, 43–87 days); 63% were male.

At least one major comorbidity (additional illness) was present in 69% of patients with prolonged COVID-19, compared with 58% of those without prolonged COVID-19. In a multivariable analysis, factors associated with prolonged hospitalization with COVID-19 were:

• Older age (70 years or older; hazard ratio [HR], 2.34)
• Relapsed or refractory lymphoma (HR, 3.12)
• Treatment with an anti-CD20 monoclonal antibody within 12 months (HR, 2.26)
• Having one or more comorbidities (HR, 1.50).

The same factors were also significantly associated with a reduced risk of overall survival, and the risk was exceptionally higher at age 70 or older (HR, 4.73). The risk was also higher for relapsed/refractory lymphoma (HR 3.34), anti-CD20 treatment (HR 2.17), and having one or more comorbidities (HR, 2.50). Although 57% of patients in the study had received B-cell-depleting treatment in the previous 12 months, the proportion was 81% among patients with prolonged COVID-19 and only 40% among those without prolonged COVID-19.

Notably, none of the patients with T-cell lymphoma (n = 8) or classical Hodgkin disease (n = 8) experienced prolonged COVID-19. Besson said: "In fact, this is another strong argument that B-cell depletion is an important risk factor for prolonged hospitalization for COVID-19".

Besson said that the main mechanism underlying the risk among these patients might be "dysfunctional immunological memory that could impair protection against reinfection and an anti-SARS-CoV-2 vaccine response".

Obesity Was Not Associated

A surprising finding of the study concerned obesity. Besson said that obesity had been identified as a leading risk factor for COVID-19 severity, yet obesity did not appear to increase the risk in the current study.

"Obesity, hypogammaglobulinemia, or lymphopenia is not significantly associated with a worse outcome. Regarding obesity, this is probably because patients with relapsed/refractory lymphoma often lose weight.” Regarding hypogammaglobulinemia or lymphopenia, "we may not have the power to establish significant associations with these factors" she added.

Balancing the Benefits of Lymphoma Treatment Against COVID-19 Risks

Regarding addressing the higher risk with anti-CD20 treatment without compromising patients' lymphoma treatment, Besson reported: "This is the most difficult point”."In the context of fluctuations in COVID-19 cases, it may be safer to continue maintenance with B-cell depletion in patients whose lymphomas are in complete remission. In any case, patients receiving these treatments should receive additional education on how to prevent infection, and their companions and healthcare teams should be vaccinated” she said.

The Choices Are Not Easy

Riches, from England, also pointed out "that depleting the humoral (fluid-based, antibody-mediated) immune system will have an effect on COVID-19 patients with some types of B-cell lymphoma, and that there is also an immune defect associated with lymphoma". Riches continued: "On the other hand, several studies have also shown some benefits for convalescent (recovering) plasma, further suggesting that antibodies are important.”

Riches agreed that the choices were not easy when it came to addressing concerns about the risk of anti-CD20 treatment. "When COVID-19 rates are high and the benefit of anti-CD20 treatment is marginal, it would be reasonable to avoid anti-CD20 treatment, for example with maintenance rituximab for follicular lymphoma."