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Objectives: Hematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. Methods: We included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant. Results: We collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). Conclusions: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks. [ABSTRACT FROM AUTHOR]

COVID-19, Haematological malignancies, rituximab, anti-CD20 monoclonal antibodies, obinutuzumab, SARS-CoV-2 infection Treatment with obinutuzumab leads to worse outcomes in haematological patients diagnosed with Omicron variant COVID-19 Keywords: anti-CD20 monoclonal antibodies; COVID-19; Haematological malignancies; obinutuzumab; rituximab; SARS-CoV-2 infection EN anti-CD20 monoclonal antibodies COVID-19 Haematological malignancies obinutuzumab rituximab SARS-CoV-2 infection 826 829 4 08/24/22 20220901 NES 220901 Abbreviations CAR-T chimaeric antigen receptor T-cell therapy CLL chronic lymphocytic leukaemia COVID-19 SARS-CoV-2 disease 2019 CRP C-reactive protein DLBCL diffuse large B-cell lymphoma FL follicular lymphoma HM haematological malignancies HSCT haematopoietic stem cell transplantation ICU intensive-care unit IQR interquartile range LOS length of stay mAB monoclonal antibodies NHL non-Hodgkin lymphoma PCR polymerase chain reaction PET positron emission tomography PFS progression-free survival RCHOP rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine (oncovin), and prednisone SMC Soroka University Medical Center T-C tixagevimab-cilgavimab VOC variant of concern Patients with haematological malignancies (HM) who fall prey to COVID-19, especially those receiving anti-CD20 monoclonal antibodies (mAB), are at a higher risk for complications, mortality, protracted disease, and relapse.1,2 Anti-CD-20 mAB became widely used for HM, especially for B-cell non-Hodgkin lymphoma (NHL). [Extracted from the article]