Omission of Anti-CD20 Antibody in Chronic Lymphocytic Leukemia during COVID-19 Pandemic: Twelve Month Course of Venetoclax Is a Safe and Effective Alternative Regimen
Authors: Shahab Aarib M , Yunus Saadia 
Published: December 2023

Introduction
The current treatment for patients with advanced stages of Chronic Lymphocytic Leukemia (CLL) is the combination of the Rituximab - an Anti-CD 20 Antibody and Venetoclax - a BCL-2 inhibitor. However, during COVID-19 Pandemic, we were concerned that the immunodeficiency state induced by anti-CD20 antibody infusions would increase the risk of COVID-19 complications. Also, we were concerned about exposing cancer patients to long term anti-neoplastic treatments when there were so many unknowns about the new Sar-CoV-2 virus. Thus, in order to minimize these deleterious effects, and long exposure to cancer treatment, the CLL treatment was modified through omitting Rituximab, and using a 12-month course of Venetoclax as a single agent, with the goal of preventing COVID complications, but still achieving durable remissions.
Methods
Between February 2020 and September 2022, 13 patients with advanced stage CLL who met the treatment criteria, were treated with single agent Venetoclax with the mean age of 77 ranging from ages 56-99 and a Male to Female ratio of 10:3. Indications of treatment were as follows: bulky lymphadenopathy (8), markedly elevated lymphocyte count (3), and bone marrow failure (2). Among these 13 patients, there were 7 treatment naive patients and 6 had previously received between 1 to 3 treatments. These treatments included: Chlorambucil-Obinutuzumab, Ibrutinib, Fludarabine-Cyclophosphamide-Rituximab, and Bendamustine-Rituximab. Following are the FISH analysis results of these patients: 13Q14, 12+, TP53- , 11Q22-. Single agent venetoclax was administered to patients as a 5 week ramp up schedule per standard dosing guidelines, with the goal being to achieve 400 mg by week 5 of the treatment. The 400 mg dosage was continued for another 11 months and patients were monitored monthly for treatment response and toxicity. After the conclusion of 12 months of treatment, patients were followed up clinically at regular intervals to monitor durability of treatment response. Patients were informed that if there was progression noted during Venetoclax treatment, a new regimen that included Anti-CD20 Antibody will be started.
Results
Eleven out of 13 patients achieved full dosage escalation to 400 mg by week 5. Of the 2 patients that did not escalate the full dose, one patient - age 99- only achieved dosage up to 100 mg due to physician discretion, and the other patient achieved dosage up to 200 mg due to extreme fatigue. Common side effects amongst the patients were fatigue and mild cytopenia whilst the toxicity overall was manageable. One patient required treatment interruption for Autoimmune Hemolytic Anemia (AIHA) and only one patient contracted COVID-19. This patient recovered, however, quickly with no complications and treatment of Venetoclax was resumed at full dosage. Temporary increase in absolute lymphocyte count was noted in 8 patients. Mild persistent anemia was shown in 2 patients at the completion of treatment and mild thrombocytopenia was present in 7 patients. Neutropenia was not observed in any patients. Overall, treatment response was noted in 12 out of 13 patients with 11 complete remission (CR) and 1 partial remission (PR). Time to response was 3 months from the start of treatment for all responding patients. All patients who achieved CR and PR remain in remission during follow up with a median remission duration of 15 months. One patient had stable disease while on treatment but progressed immediately after discontinuation of Venetoclax. This patient then received the combination of Obinutuzumab-Acalabrutinib and achieved complete remission.
Conclusion
Thus, we can conclude that a 12-month course of Venetoclax administered without anti-CD 20 antibody, is an effective treatment regimen in advanced stage CLL. The avoidance of the anti-CD 20 antibody resulted in preservation of the immunity as noted in the one patient who contracted COVID-19 during treatment but recovered quickly from infection without any COVID-19 associated complication. We believe that although Rituximab with Venetoclax remains the standard of care in advanced stage CLL, but in unusual circumstances such as during the COVID-19 pandemic, short, limited course of single agent Venetoclax is a viable option of treatment to achieve durable remission.