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

Author:

Shafat Tali1234ORCID,Grupel Daniel56,Porges Tzvika7,Abuhasira Ran2,Belkin Ana89,Deri Ofir10,Oster Yonatan56,Zahran Shadi56,Horwitz Ehud56,Horowitz Netanel A.11ORCID,Khatib Hazim11,Batista Marjorie Vieira412,Cortez Anita Cassoli13,Brosh‐Nissimov Tal1415,Segman Yafit1516,Ishay Linor1718,Cohen Regev1718,Atamna Alaa419,Spallone Amy34,Chemaly Roy F.34,Ramos‐Ramos Juan Carlos420,Chowers Michal2122,Rogozin Evgeny23,Oren Noga Carmi23,Keske Şiran424,Barchad Orit Wolfovitz25,Nesher Lior14ORCID,

Affiliation:

1. Infectious Diseases Institute, Soroka University Medical Center, and the Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva Israel

2. Clinical Research Center, Soroka University Medical Center, and the Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva Israel

3. Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston Texas USA

4. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Respiratory Viruses (ESGREV) Basel Switzerland

5. Department of Clinical Microbiology and Infectious Diseases Hadassah Medical Center Jerusalem Israel

6. Faculty of Medicine Hebrew University Jerusalem Israel

7. Hematology Department, Soroka University Medical Center, and the Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva Israel

8. Internal Medicine D and Infectious Diseases Unit Sheba Medical Center Ramat‐Gan Israel

9. Sackler Faculty of Medicine Tel Aviv University Ramat‐Aviv Israel

10. Internal Medicine T Sheba Medical Center Ramat‐Gan Israel

11. Department of Hematology and Bone Marrow Transplantation Rambam Health Care Campus Haifa Israel

12. Department of Infectious Diseases AC Camargo Cancer Center São Paulo São Paulo Brazil

13. Department of Hematology and Cell Therapy AC Camargo Cancer Center São Paulo São Paulo Brazil

14. Infectious Diseases Unit Samson Assuta Ashdod University Hospital Ashdod Israel

15. The Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva Israel

16. Hematology Institute Samson Assuta Ashdod University Hospital Ashdod Israel

17. Rappaport Faculty of Medicine Technion Haifa Israel

18. Hillel Yaffe Medical Center Hadera Israel

19. Infectious Diseases Unit, Rabin Medical Center Beilinson Hospital Petah Tikva Israel

20. Infectious Disease Unit Internal Medicine Service. CIBERINFEC. Hospital Universitario La Paz Madrid Spain

21. Meir Medical Centre Kfar Saba Israel

22. Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

23. Infectious Diseases unit Shamir (Assaf Harofeh) Medical Center Be'er Ya'akov Israel

24. Department of Infectious Diseases VKV American Hospital Istanbul Turkey

25. Infectious Disease Unit Shaare Zedek Medical Center Jerusalem Israel

Abstract

AbstractObjectivesHematological 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.MethodsWe 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.ResultsWe 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).ConclusionsDespite 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.

Publisher

Wiley

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