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Department of Medicine
Harvard Medical School
Jacob D. Soumerai, MD, has disclosed that he has received funds for research support from BeiGene, BostonGene, Genentech/Roche, GlaxoSmithKline, and TG Therapeutics and consulting fees from AbbVie, AstraZeneca, and Verastem.
With the first 6 months of the COVID-19 pandemic behind us, I can share how my management of patients with chronic lymphocytic leukemia (CLL) has evolved, how I apply key data on COVID-19 risk in patients with CLL, emerging data that may impact therapy selection, and what I anticipate the coming months will bring for clinicians and for patients with CLL.
How My Practice Has Changed After 6 Months
Triaging Patients for Virtual vs Clinic Visits
When the COVID-19 pandemic started in March 2020, our clinics in Boston were hit by both the direct effects of COVID-19 on our patients, and the indirect, societal effects—meaning patients often could not attend in‑person visits. We knew little about COVID-19 at the time, and so we conducted many visits virtually or via telephone. This was often acceptable for patients without a clear need to be in the clinic (eg, patients with ongoing response to oral CLL treatment for whom virtual review of history and local blood work may be sufficient), and some components of the physical examination can be performed virtually! While this may be sufficient for a patient with predominantly leukemic-phase disease, for whom the history and blood counts tell most of the story, virtual care may be less effective for those with disease in the lymph nodes and spleen which must be measured by physical examination. When conducting a virtual visit, I have a very low threshold to bring my patients back into the clinic.
Minimizing Risk During Clinic Visits
I am very lucky to care for patients with CLL and lymphoma at an institution with a spectacular administration and top-notch infection control practices. I have not had a single patient acquire COVID‑19 because they saw see me in the clinic. As a result, I am increasingly bringing my patients into the clinic, although I continue to conduct some patient visits virtually. This may change based on the COVID-19 infection rate in our community, but we are now armed with knowledge about COVID-19 and, of importance, all the appropriate infection control practices are in place at our clinic to protect patients should the infection rate climb again.
Counseling Patients on COVID-19
At this time, when a patient with CLL requires therapy, the COVID-19 pandemic does not typically impact CLL treatment selection, which is driven by discussions with my patients (e.g. time-limited vs continuous therapy, comorbidities, etc). However, COVID-19 continues to dominate our daily lives, and is a primary concern for all of our patients. We spend considerable time discussing COVID-19, what we know and do not know about COVID-19 risk in patients with CLL, and how to mitigate COVID-19 risk.
What We Know About CLL and COVID-19 Risk After 6 Months
Over the past 6 months, we have gained some insights into how COVID-19 intersects with CLL and treatments for CLL. Retrospective data suggest that patients with cancer, including CLL, appear to have an increased risk of severe COVID‑19. However, I remind my patients that there is a significant heterogeneity among patients with CLL. In one clinic, I may see one patient with minimal disease burden who has been on active surveillance for the better part of a decade, another who was previously exposed to cytotoxic chemotherapies (eg, fludarabine or bendamustine) and is presenting with recurrent adenopathy, and yet another who is receiving a novel targeted agent. I would bet that the risks of complications from COVID‑19 are different for each of these patients, although this level of granular detail is not known. I tell my patients that, in general, CLL appears to be associated with an increased risk of severe complications from COVID-19 infection, but that the data have limitations and the true risk of severe complications and death is not known.
A retrospective multicenter study of COVID-19 in CLL conducted by Anthony Mato and colleagues showed that COVID-19 mortality in patients with CLL is associated with increasing age and comorbidities. Interestingly, these are the same risk factors that predict more severe COVID-19 infections among COVID-19–infected people who do not have CLL. I was especially interested to learn that CLL-related hypogammaglobulinemia does not appear to affect COVID-19. At present, the COVID-19 health crisis is not an indication to give empiric IVIg for hypogammaglobulinemia. I advise IVIg supplementation for patients with CLL who develop symptomatic hypogammaglobulinemia (eg, associated with recurrent or severe sinopulmonary or skin/soft tissue infections).
Intriguingly, a European study by Scarfò and colleagues suggested that treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib might result in favorable COVID-19 outcomes among patients with CLL. However, these data are limited by their retrospective/observational nature and subject to confounding factors. Perhaps ibrutinib treatment is associated with other patient characteristics which are associated with a lower risk of severe complications from COVID-19 (eg, certain comorbidities that might preclude ibrutinib therapy). Additionally, Anthony Mato and colleagues found no difference in COVID-19 outcomes with BTK inhibitor treatment, although the BTK inhibitor was held for most patients in this series. We await data from the ongoing placebo-controlled, randomized trials evaluating ibrutinib, acalabrutinib, and zanubrutinib in patients with COVID‑19 and respiratory distress.
Should these data impact treatment selection for patients with CLL who require therapy? I do not believe so. These are interesting clinical observations which rightly serve as the basis for ongoing randomized experiments to establish whether there is a role for BTK inhibition in COVID-19 infection. However, these data do not impact my CLL treatment recommendations, which are driven by discussion with each patient about whether they value time-limited vs continuous therapy and whether there are comorbidities precluding a particular therapy. For patients already on a BTK inhibitor for CLL who develop COVID-19, there is ongoing debate about whether to hold or continue the BTK inhibitor. Unless the patient would otherwise require a treatment hold based on the severity of toxicity as described in the package insert, I am inclined to keep my patients on the BTK inhibitor.
Even though the rate of COVID-19 infection is lower now in Boston, we are planning ahead. Our community has been very diligent with public health measures such as mask wearing and social distancing which has resulted in fewer infections, and I hope that these community efforts blunt or ward off another surge like we experienced here in Boston during the spring. That said, I am optimistic that we are much better positioned to react to a second surge. After all, we know more about COVID-19 and how it is spread, we have more capacity to test for COVID-19 than we did in the spring, and we have established hospital-wide systems and well-oiled infection control practices that protect our patients with CLL from this infection.