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Associate Professor of Medicine
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Division of Hematology/Oncology
Northwell Health System
Lake Success, New York
Jacqueline Barrientos, MD, MS, has disclosed that she has received funds for research support from Oncternal; consulting fees from AstraZeneca, Bayer, Genentech, Gilead Sciences, and Sandoz; and other financial or material support from Janssen.
COVID‑19 is a new disease and we are all learning as we go. When the pandemic hit Western Europe and the United States, several of the professional societies, in an attempt to improve the outcomes of our patients with cancer, recommended delaying any interventions, whenever possible, and for patients to receive supportive care only, and this is the approach we have been taking with our patients with chronic lymphocytic leukemia.
We have to take into account that patients with CLL, even without any history of previous therapy, are always at a high risk for infection, and in fact, poor outcomes can result from any type of infection, which is why we strongly recommend that our patients with CLL receive flu, pneumonia, and shingles vaccines to mitigate the risk of infection and complications that can result. Unfortunately, with COVID‑19, we don't have a vaccine yet and we know that, even in the general population, COVID-19 can have serious outcomes and that it is a very difficult disease to manage in patients without comorbidities. Patients with CLL are, on average, diagnosed in their 70s, and by the time that they are diagnosed, they frequently have multiple other comorbidities, such as diabetes, obesity, hypertension, and cardiac disease. All of these comorbidities are associated with worse outcomes with coronavirus infection. Hence, our recommendation has always been to try to avoid therapy for CLL whenever possible.
Managing CLL in New York City During the Peak COVID-19 Crisis
That said, however, some of our patients absolutely cannot wait for therapy. For example, one of my patients was previously completely refractory to any chemo‑immunotherapeutic approaches. She had been treated with a BTK inhibitor but developed intracranial bleed and needed therapy, so we had to treat her with venetoclax—this is a drug that requires hospitalization to initiate in patients who are at high risk for tumor lysis syndrome. This was at the time when COVID-19 was at its peak in New York City. We did manage to avoid hospitalizing her and successfully treated her as an outpatient, but it was very difficult because it required the careful collaborative efforts of several medical providers and the laboratories with the knowledge that, at any time, she could develop tumor lysis syndrome.
So we have ways to mitigate potential toxicities that can come from treating CLL, but unfortunately, in the era of COVID-19, these are more difficult when you have a medical system that is under strain. At the time that we treated this patient, our hospital system had 3500 patients hospitalized with COVID-19.
New Data on Outcomes From Coronavirus Infection in Patients With CLL
Our group published data on 5700 patients with CLL and COVID-19, and there were many fatalities among those patients who required intervention. Our goal has always been to try to avoid exposure of COVID-19 to our patients with CLL, and if we can avoid treating them for their CLL, we could potentially help them survive until we have more resources available to treat COVID-19, both medically and also therapeutic interventions. At the time that we in New York City experienced our peak in COVID-19 cases, remdesivir was not available to us and we had no data on the outcomes of patients treated with dexamethasone. We also didn’t have access to convalescent plasma, which is now available in other states that are experiencing a peak in COVID-19 cases.
Although our knowledge of COVID-19 and treatment strategies have improved, we still have to face the fact that, invariably, this disease can affect patients in a very heterogeneous way and we do not know who is going to be severely affected. Anthony Mato, MD, MSCE, recently published the outcomes of 198 patients with CLL who were hospitalized with COVID-19, and unfortunately, the case fatality rate was approximately 33%. Those are difficult odds for any patient with CLL so we strongly recommend that these patients avoid any interactions with other patients or people who may have any potential for COVID-19 diagnosis or exposure, that is, stay at home as much as possible.
Treatment Selection for Patients Who Need Therapy During COVID-19
In my practice, we mitigate the potential exposure for COVID-19 at our clinic by doing a lot of telehealth visits. We also offer our patients with CLL in‑home blood draws to minimize the exposure to other people at the laboratory facilities, and as much as possible, we try to minimize contagion at our center by testing all of our patients for COVID-19 by PCR. Patients who test negative can be treated in the COVID‑19–negative room and those who test positive are isolated in a different room where they can receive their therapy.
We definitely try to avoid infusional therapy as much as possible, such as monoclonal antibodies (rituximab, obinutuzumab), which are usually widely used in combination with some of the targeted agents. Anecdotally, in my clinic, some of the patients experience a prolonged lymphocytopenia or neutropenia, and with COVID-19, they take longer to clear the virus. For example, one of my patients was receiving chemo‑immunotherapy because he had a Richter’s transformation right before the COVID-19 pandemic reached New York. After 1 cycle, the Richter’s went into remission, and just before the second cycle, he developed fever and cough and tested positive for COVID-19. It took 10 weeks to clear the virus, and he was still having a lot of difficulty breathing and ambulating from the deconditioning and weight loss that he suffered from the virus. He received his second cycle a week ago, and he is now functionally back to his baseline and is COVID-19 negative, but he still has not produced antibodies.
As you may be aware, most of our patients with CLL have very poor antibody production, which puts them at a higher risk. Indeed, we are observing that very few of our patients with CLL who recover from COVID-19 develop antibodies. As a result, some of our patients with CLL require immunoglobulin infusions monthly. Therefore, our primary goal is to first delay any introduction of new therapies as much as possible, and secondly, if the patient requires therapy, we try to avoid anything that could cause myelosuppression because that can potentially put them at a higher risk of contracting COVID-19.
BTK Inhibitors in the Treatment of Severe COVID-19
There are some promising data that BTK inhibitors can help to avoid the severe complications from COVID-19. There was a small study published recently by Steve Treon, MD, PhD, and colleagues on Waldenström macroglobulinemia, where a small group of patients had been receiving the BTK inhibitor ibrutinib, and they avoided the severe pulmonary complications from COVID-19. One of the patients had been on a lower dose of the BTK inhibitor and when the patient was intubated, the dose of the BTK inhibitor was increased and the patient was successfully extubated within 48 hours.
There is another recent publication from Mark Roschewski, MD, and colleagues at the NIH. They treated patients with COVID-19 who did not have CLL with the BTK inhibitor acalabrutinib, and in these patients, they were able to successfully reduce the severity of respiratory complications.
In my practice, we talk about these recent publications and about my anecdotal experience of patients receiving a BTK inhibitor. In our experience, we do not stop BTK inhibitor therapy if a patient contracts COVID‑19. Although there are some data that BTK inhibition can increase the risk for other infections, the data for their efficacy at mitigating the severe pulmonary and inflammatory complications of COVID-19 are promising, and I do have a predilection to choose a BTK inhibitor for a treatment‑naive patient with CLL who requires initiation of therapy during the COVID-19 pandemic. This is not only due to the potential for preventing the pulmonary complications, but also because many patients receiving BTK inhibitor therapy will not require hospitalization, whereas a treatment like venetoclax does require hospitalization for patients at intermediate or high risk for tumor lysis syndrome. In addition, many of the patients whom I start on a BTK inhibitor will only need laboratory studies and can be managed via telehealth visits, further minimizing their risk for exposure.
How do you minimize the risk of exposure to COVID-19 in your patients with CLL? Does the current pandemic affect your choice of therapy in patients who cannot delay the start of their treatment?