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

Tali Shafat*, Daniel Grupel, Tzvika Porges, Ran Abuhasira, Ana Belkin, Ofir Deri, Yonatan Oster, Shadi Zahran, Ehud Horwitz, Netanel A. Horowitz, Hazim Khatib, Marjorie Vieira Batista, Anita Cassoli Cortez, Tal Brosh-Nissimov, Yafit Segman, Linor Ishay, Regev Cohen, Alaa Atamna, Amy Spallone, Roy F. ChemalyJuan Carlos Ramos-Ramos, Michal Chowers, Evgeny Rogozin, Noga Carmi Oren, Şiran Keske, Orit Wolfovitz Barchad, Lior Nesher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageAmerican English
Article numbere6997
JournalCancer Medicine
Issue number3
StatePublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.


  • anti-CD20 monoclonal antibodies
  • COVID-19
  • hematological malignancies
  • obinutuzumab
  • rituximab


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