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Obinutuzumab is a type II humanized anti-CD20 antibody of the IgG1 subclass that mediates B-cell lysis by direct cell death and by antibody-dependent cell -mediated toxicity. The treatment with GA 101 (single agent or combined) causes a potent overall B-cell depletion that may compromise the antiviral immunity and augment the tendency to severe pulmonary complications.

We conducted a one year retrospective study of all the patients hospitalized in our Service of Hematology, (Department of internal Medicine, UHC ' Mother Teresa' ) being diagnosed with Follicular Lymphoma and Chronic Lymphoid Leukemia under treatment with Obinutuzumab to  evaluate and identify all the COVID-19 positive patients and to evaluate their outcome.

We reviewed the data of all the patients >18 years old, diagnosed with Follicular Lymphoma and Chronic Lymphoid Leukemia, hospitalized in our Service of Hematology from January 2020 to January 2021 under treatment with Obinutuzumab (single agent or combined). The positivity of COVID-19 infection was demonstrated through positive PCR- based test (nasopharyngeal swab). Chest scan was performed to access the severity of pulmonary involvement from SARS-COV-2.

A total number of 25 (100%) patients on Obinutuzumab treatment were identified. 20 (80%) patients were diagnosed with CLL and 5 (20%) patients were diagnosed with FL. The median age for CLL patients resulted 61,8 years (18-80 yrs) and the median age for FL resulted 50,8 years ( 18-80 yrs). 14 (70%) of CLL patients were classified as high- risk CLL and 6 (30%) as intermediate-risk CLL. All the FL were classified as high -risk FL. 60% of all the patients were without comorbidities at the moment of the diagnosis ( 11 CLL and 4 FL patients) and 40% has two or more comorbidities at diagnosis. 6 CLL patients and 4 FL patients were on 1st line Obinutuzumab, 10 CLL patients and 1 FL patient were on 2nd line Obinutuzumab, and 4 CLL patients were on 3rd line Obinutuzumab. All the patient were at the moment of starting the treatment with Obinutuzumab with ECOG 0-1. No therapy related complications were found.
32% (8) of all the patients receiving Obinutuzumab were without comorbidities and ECOG 0-1 at the moment of getting infected with SARS-COV-2 (5 high-risk CLL patients and 3 FL patients) and developed severe COVID-19 pneumonia 5 to 9 days after getting infected with rapid critically severe clinical picture evolution. The median age of the patients infected with COVID-19 resulted 55,6 years (24- 67years), and the male:female ratio resulted 1,6:1. They were all treated in the ICU and unfortunately none of them survived more than 30 days-hospitalization time. The COVID-19 mortality in this cohort was 100%.

The introduction of new anti-CD20 antibodies as Obinutuzumab in the treatment of CLL and Follicular Lymphoma undoubtedly is a milestone in the treatment history of Lymphoid Neoplasms, being 1,5 to 2,5 times more effective than Rituximab, prolonging the overall survival of the patients and giving a great impact on the decourse of the disease. With our study (a very small cohort study) we demonstrate that getting infected with SARS-COV-2 is not related to the treatment with Obinutuzumab or other chemotherapies, but the patients treated with Obinutuzumab (single agent or combined) develop a very severe COVID-19 clinic. If this is biologically caused or is just a casualty finding is still to be studied. Previous studies have demonstrated almost the same results but further studies are needed to evaluate this findings.