1201 - Impact of COVID-19 in patients with Chronic Lymphocytic Leukemia treated with venetoclax: a possible role of the association to anti-CD20 antibody? A multicentre SEIFEM study.

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), has led to a significant increased morbidity worldwide. The severity of the disease can vary between patients, with history of cancer and administration of antileukemic treatment were associated with worse outcome.
A recent meta-analysis showed a high case fatality rate in hospitalized patients with hematological malignancies. Published reports indicated high rates from 27.3% to 35% also in chronic lymphocytic leukemia patients (CLL) patients.
The aim of our study was to evaluate the impact of COVID-19 in CLL patients treated with venetoclax.
Methods. The retrospective multicenter study included CLL patients treated since 2017 with venetoclax single agent until progression or toxicity or venetoclax plus anti-CD20 antibody (mainly rituximab as part of VR protocol for 24 months or obinutuzumab as part of VO protocol for 12 months).
Results. We found 114 infections from SARS-CoV-2 in 96 patients out of 287 patients with CLL who received venetoclax during the study period. Basal characteristics of the 96 patients who experienced COVID-19 were compared to those of the 191 patients who did not experience the infection (data are shown in Table 1). Patients of the first group did not show more comorbidities in terms of CIRS, nor renal and pulmonary impairment. Unexpectedly patients without COVID-19 experienced more previous infections in the 12 months before the beginning of the treatment with venetoclax; they also were exposed to a high rate of prophylaxis as immunoglobulin and antiviral drugs.
We noted that in the group of COVID-19 a higher rate of patients received venetoclax plus anti-CD20 antibody (64.4% in the group of COVID-19 vs 38.7% in the group without COVID-19). The rate of vaccination was high in both: 87% in the first and 74.8% in the second with a median of 3 doses each.
Analyzing characteristics of the 114 infections we distinguished 64 grade 1-2 COVID-19 and 50 grade 3-4 COVID-19.
Patients with grade 1-2 COVID-19 resulted positive for a median time of 10 days (range 5-52), 87% of the patients were vaccinated. Exposure to anti-CD20 antibody associated to venetoclax was present in 61% of the cases. No treatment was administered in 33.3% of the cases, nirmatrelvir/ritonavir was used in 23% of the cases, remdesivir in 18%. Prophylaxis with tixagevimab/cilgavimab was administered in 22.2% of the patients.
Patients with grade 3-4 COVID-19 resulted positive for a median time of 18 days (range 5-97), 86% of the patients were vaccinated. Exposure to anti-CD20 antibody associated to venetoclax was present in 66% of the cases. Remdesivir was chosen as treatment in 49% of the cases, nirmatrelvir/ritonavir in 24.4%. Prophylaxis with tixagevimab/cilgavimab was administered in 21.9% of the patients. Venetoclax was withdrawn in 71.5%, and in more than 80% of whom venetoclax was administered together with an anti-CD20 antibody. In most of the cases the discontinuation was only temporary.
Sixty-seven % of the patients required hospitalization due to COVID-19, the median time of recovery was 15 days, and 20.7% of them needed intensive care unit admission.
Among the 96 patients with COVID-19, 18 patients died, 10 died due to COVID-19, 7 were exposed to anti-CD20 antibody, 3 had a previous grade 1-2 COVID-19, but none experienced a SARS-CoV-2 infection before treatment with venetoclax. All were vaccinated with at least 3 doses except one patient who was not vaccinated but was infected and died in 2020. The rate of mortality due to COVID-19 was 10.4% considering patients who were infected by SARS-CoV-2, but 20% among patients with severe grade 3-4 infection.
Conclusions. This is a real-life study on 287 patients affected by CLL treated with venetoclax with the aim to describe COVID-19 in this cohort.
The analysis found a significant rate of infections (33.4%), most of grade 1-2, without a high rate of mortality. The increased rate (70%) of venetoclax discontinuation during COVID-19 was a physician choice to decrease the risk of complications since the association of anti-CD20 antibody to venetoclax seems to have a role in the risk of COVID-19.