Treatment with obinutuzumab leads to worse outcomes in haematological patients diagnosed with Omicron variant <scp>COVID</scp>‐19

Shafat, Tali; Grupel, Daniel; Porges, Tzvika; Levi, Itai; Yagel, Yael; Nesher, Lior

doi:10.1111/bjh.18315

Cited by 12 publications

(20 citation statements)

References 9 publications

(13 reference statements)

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“…This immune dysregulation drives CLL patients to develop more severe courses of COVID-19 infections especially when under additional immunosuppression by chemoimmunotherapy (10). Differential risk of adverse clinical outcomes has been reported depending on the type of CLL treatment especially with anti-CD20 monoclonal antibodies, while other targeted therapies might have protective effects against COVID-19 by attenuating hyperinflammatory responses (11,12). Also, differential risk of adverse clinical outcomes has been described among patients with systemic rheumatic disease based on the type of biological agents received (13).…”

Section: Discussionmentioning

confidence: 99%

ProlongedSARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy

Papanikolopoulou

Thimis

Antonogiannaki

et al. 2023

In Vivo

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Background/Aim: Anti-CD20-depleting monoclonal antibodies predispose patients to the development of severe disease of SARS-CoV-2 infection. These antibodies are given as backbone or maintenance therapy in patients with hematological malignancies and rheumatology diseases, inducing effective B-cell depletion along with antibodydependent cell-mediated cytotoxicity (ADCC) and disrupting infection-protective antibody responses. Case Report: We describe two cases of prolonged SARS-CoV-2 infection with common features, in two patients receiving anti-CD20 therapies, the first for chronic lymphocytic leukemia (CLL) and the second for rheumatoid arthritis (RA). For CLL patient, despite administration of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 43 days, with resolution and lymphocyte recovery from day 33. For RA patient, despite administration of two courses of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 47 days, without resolution and lymphocyte recovery, leading to a fatal outcome due to acute respiratory distress syndrome (ARDS) and unspecified sepsis. Conclusion: These two cases highlight the risk for persistent SARS-CoV-2 infection in patients treated with anti-CD20 monoclonal antibodies and support a role for cellular immunity recovery for disease control.

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Section: Discussionmentioning

confidence: 99%

ProlongedSARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy

Papanikolopoulou

Thimis

Antonogiannaki

et al. 2023

In Vivo

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“…COVID‐19 recurrence, proliferation, and severity have been reported in patients treated with anti‐CD20 monoclonal antibodies. 1 After infection with SARS‐CoV‐2, the seroconversion rate is only 59% in patients previously treated with anti‐CD‐20 antibodies. 3 In patients with hematologic malignancies who were infected with omicron variants, treatment with obinutuzumab resulted in worse clinical outcomes than treatment with rituximab.…”

Section: Discussionmentioning

confidence: 99%

“… 3 In patients with hematologic malignancies who were infected with omicron variants, treatment with obinutuzumab resulted in worse clinical outcomes than treatment with rituximab. 1 …”

Section: Discussionmentioning

confidence: 99%

“…Patients with coronavirus disease 2019 (COVID‐19) treated with anti‐CD20 antibodies have worse outcomes and prolonged symptoms. 1 However, no evidence‐based treatment is available for these patients. Herein, we report a case of prolonged COVID‐19 that was treated with tixagevimab/cilgavimab.…”

Section: Introductionmentioning

confidence: 99%

“…Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an endemic virus that affects people worldwide. Patients with coronavirus disease 2019 (COVID‐19) treated with anti‐CD20 antibodies have worse outcomes and prolonged symptoms 1 . However, no evidence‐based treatment is available for these patients.…”

Section: Introductionmentioning

confidence: 99%

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A case of prolonged COVID‐19 treated with tixagevimab/cilgavimab

Shimizu

Shirasaki

Okafuji

et al. 2023

Respirology Case Reports

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A 54‐year‐old woman presented to our hospital with a fever and cough. The patient had a medical history of follicular lymphoma treated with obinutuzumab. She was infected with an omicron variant of coronavirus disease 2019 and developed viral pneumonia. Antibiotics, molnupiravir, sotrovimab, and prednisolone were administered but were ineffective. The patient's symptoms and pneumonia persisted. She could not produce antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) because she was administered obinutuzumab. Finally, when we administered 300 mg of tixagevimab and cilgavimab, pneumonia immediately improved. However, the infection was prolonged for more than 4 months. Patients treated with anti‐CD20 monoclonal antibodies may have a prolonged SARS‐CoV‐2 infection. In such cases, tixagevimab/cilgavimab may be effective.

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

Shafat,

Grupel,

Porges

et al. 2024

Cancer Medicine

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ObjectivesHematological 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.

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Treatment with obinutuzumab leads to worse outcomes in haematological patients diagnosed with Omicron variant COVID‐19

Cited by 12 publications

References 9 publications

ProlongedSARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy

ProlongedSARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy

A case of prolonged COVID‐19 treated with tixagevimab/cilgavimab

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

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