COVID-19 infection in patients with follicular lymphoma and related indolent B-cell lymphomas receiving anti-CD20 monoclonal antibody maintenance therapy

Introduction: Coronavirus disease 2019 (COVID-19) poses significant risks to immunocompromised individuals. Patients receiving maintenance therapy with anti-CD20 monoclonal antibodies for follicular lymphoma (FL) may be especially vulnerable because of prolonged B-cell depletion. However, data from Japan, particularly from the later stages of the pandemic, remain limited. This study aimed to investigate the incidence, severity, duration, mortality, and treatment discontinuation associated with COVID-19 in this population. Methods: We retrospectively analyzed all consecutive 72 patients with FL or related indolent B-cell lymphomas, including transformed FL, who received anti-CD20 maintenance therapy (rituximab or obinutuzumab) at our institute between January 2020 and September 2023. All patients had an indolent lymphoma background. Data on clinical features, laboratory values, disease severity at initial diagnosis according to Ministry of Health, Labour and Welfare guidelines, hospitalization, outcomes, duration of PCR positivity (>21 days defined as prolonged), and maintenance therapy continuation were reviewed. Fisher’s exact test was used for analysis. Results: Among the 72 patients (median age: 72 years), 16 (22.2%) developed COVID-19. Of these, 5 had received rituximab and 11 obinutuzumab. The median lymphocyte count at infection was 498/μL; no patient had serum IgG <500 mg/dL. Eight infected patients developed oxygen-requiring disease at initial assessment (50.0% of infected patients; 11.1% overall). Prolonged infection occurred in 9 patients (56.3% of infected patients; 12.5% overall). All four deaths were COVID-19-related and occurred in obinutuzumab recipients (25.0% of infected patients; 5.6% overall). Lymphocyte count <200/μL was associated with mortality (p = 0.027), although this finding should be interpreted cautiously because of the small number of events. Maintenance therapy was discontinued in 5 of 8 patients infected during therapy. Conclusion: COVID-19 infection during anti-CD20 maintenance therapy led to severe illness and prolonged viral shedding in some cases. Severe lymphopenia may be a potential risk marker for mortality, but this finding should be interpreted cautiously because of the exploratory nature of the analysis.