An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

Objectives: Hematological malignancy (HM) patients treated with anti- CD20 monoclonal antibodies are at higher risk for severe COVID- 19. A previous singlecenter 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 severecritical 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.