2654. International Multi-Center Study Comparing the Effect of Obinutuzumab or Rituximab Treatment in Hematological Patients on COVID-19 Outcomes During the Omicron Surge

BACKGROUND: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19 and adverse outcomes. A previous single-center study showed worse outcomes in patients treated with obinutuzumab than those treated with rituximab. METHODS: This is an international, multi-center population-based study across 15 centers (Israel, USA, Spain, Brazil, and Turkey). We included patients with HM treated with obinutuzumab or rituximab between December 2021 and June 2022, when Omicron lineage variants were dominant. RESULTS: We collected data on 1049 patients, of which 761 (73%) received rituximab. Of the rituximab group, 191 contracted COVID-19 compared to 104 in the obinutuzumab group (fig 1). COVID-19 patients in the obinutuzumab group were younger (mean age of 61±11.7 vs. 64 ±14.5 years, p=0.037), had more favorable HM diagnosis (aggressive lymphoma: 7.7% vs. 67.0%, p< 0.001), and were on maintenance therapy at COVID-19 diagnosis (62.4% vs. 36.2%, p< 0.001). Severe COVID-19 occurred in 31.7% (n=33) of patients in the obinutuzumab group and in 22.0% (n=42) in the rituximab group (fig 2). In a multivariable analysis for severe COVID-19, adjusted for Charlson co-morbidity index, HM status, and tixagevimab/cilgavimab (T-C) prophylaxis, we observed an odds ratio of 2.06 (95% CI 1.11-3.81, p=0.021) for obinutuzumab treatment. Prophylaxis with T-C was protective (OR 0.32 95% CI 0.10-0.99, p=0.048). In the secondary outcomes analysis, more patients with COVID-19 in the obinutuzumab were hospitalized (51.9% vs. 35.1% p=0.005), required ICU admission (13.5% vs.5.3%, p=0.014), with a non-significant difference in COVID-19 related mortality (n=11, 10.6% vs. n=12, 6.3%, p=0.189). [Figure: see text] [Figure: see text] CONCLUSION: This international, multi-center cohort study demonstrates that despite younger age and more favorable HM diagnoses, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit when considering obinutuzumab therapy for HM patients and re-emphasize the crucial role of pre-exposure prophylaxis with effective anti-SARS-CoV-2 monoclonal antibodies during high transmission in the community. DISCLOSURES: Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant