Since March 2020 when the WHO declared COVID19 a pandemic, the questions I have heard the most in my clinic from patients living with CLL are: Do I have a higher risk of getting infected? Do I need to stop my CLL treatment to prevent COVID19? If I get infected, should I stop my CLL treatment?
The most truthful answer to these questions, at this moment, is: We don’t know for certain. This is a new disease and we are just beginning to understand how it works, how it spreads and what can be done. Thankfully, the same questions have been in the minds of CLL physicians and oncologists across the world, and evidence is being collected on how to best deal with the situation.
A recent publication from China1 reported on clinical characteristics and outcomes (death, ICU admission, development of severe/critical symptoms, and utilization of invasive mechanical ventilation) of patients affected by the SARS-CoV-2 coronavirus for 105 hospitalized patients with cancer and 536 patients without cancer. When compared to the population without cancer, patients with cancer had a higher chance for respiratory distress at presentation (14.3% vs 6.2%) but did not differ in age, sex and other presenting symptoms. Compared with COVID-19 patients without cancer, patients with cancer had higher risk of death (2.3x), higher risk of ICU admission (2.8x), higher rates of developing at least one severe or critical symptom (2.8x) and higher chances of needing invasive mechanical ventilation (2x). Although patients with hematological cancers were the least common within the studied population (8%), they presented high-risk for death (33%), ICU admission (44%) and mechanical ventilation (22%). This may point to the fact that patients with hematological malignancies commonly receive treatments that may impair the activity of the immune system, therefore increasing the risk for worse outcomes when infected.
However, none of the patients in this series presented with CLL. The Hospital Clinic in Barcelona reported on the course of 4 patients with CLL presenting with COVID192. Out of 420 living patients registered with CLL at this hospital, only 4 (0.95%) have presented with symptomatic COVID19. Two of these patients have been previously treated for CLL. Of the 4 patients, 3 improved with supportive care within 8-10 days, and the last one improved after 24 days of experimental therapy for COVID19. No patient required ICU admission or mechanical ventilation. It is speculated that severe complications of COVID19, particularly pneumonia and respiratory failure, are dependent on a competent immune system, as the lung infection leads to recruitment of pro-inflammatory immune cells that may lead to severe forms of the disease. The baseline immunodeficiency secondary to CLL may contribute to the low symptom burden seen in these cases, though this is just theoretical.
Interestingly, there have been a few case reports of patients with CLL or low-grade Lymphoma that were being treated with BTK inhibitors (such as ibrutinib, acalabrutinib, zanubrutinib, etc) who presented COVID19 but did not progress to severe forms of the disease3,4. Particularly, one case report of a patient with Waldenstrom’s Macroglobulinemia (a low-grade lymphoma) who was taking low doses of ibrutinib due to side effects, and presented with COVID19, progressing to respiratory failure and mechanical intubation, presented with immediate and significant improvement once ibrutinib was increased to full dose. Several studies are underway with different BTK inhibitors, specifically looking at their role in the treatment of COVID19.
To summarize, the current moment is one of caution. People living with CLL should follow local recommendations for social distancing, thorough hand-washing, mask using in public and minimizing utilization of non-essential services, as to decrease risks of being infected with SARS-CoV-2 and developing COVID19. For those who unfortunately get infected, the moment is not one of despair though. Each case must be individually evaluated for appropriate management, and continuation vs discontinuation of therapy is an important discussion that should involve their primary hematologist/oncologist.
- Dai M, Liu D, Liu M, et al. Patients with Cancer Appear More Vulnerable to SARS-COV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020.
- Baumann T, Delgado J, Montserrat E. CLL and COVID-19 at the Hospital Clinic of Barcelona: an interim report. Leukemia. 2020.
- Thibaud S, Tremblay D, Bhalla S, Zimmerman B, Sigel K, Gabrilove J. Protective Role of BTK Inhibitors in Patients with Chronic Lymphocytic Leukemia and COVID-19. Br J Haematol. 2020.
- Treon SP, Castillo J, Skarbnik AP, et al. The BTK-inhibitor ibrutinib may protect against pulmonary injury in COVID-19 infected patients. Blood. 2020.
Alan Skarbnik, MD
Director, Lymphoproliferative Disorders Program
Novant Health Cancer Institute