As part of a series of interviews with cancer experts during the COVID-19 pandemic, The ASCO Post spoke with Hagop Kantarjian, MD, Professor and Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, about the impact of the pandemic on treatment of patients with leukemia. Editorial advisor for The ASCO Post, Syed A. Abutalib, MD, prepared the questions for Dr. Kantarjian.
Hagop Kantarjian, MD
View From MD Anderson
How has COVID-19 impacted the treatment of patients with cancer at MD Anderson?
Much of what I will discuss is based on educated guesses rather than solid data. Knowledge is continually evolving as we gain experience during the COVID-19 crisis with our patients and patients at other institutions with greater exposure to COVID-19, for example in New York City.
Health-care facilities need to have widespread availability to COVID-19 testing, so we can test all persons with suspected COVID-19 infection and be able to isolate them if they are infected. We need to have extensive access to both the nasal swab test and the serum test for IgG.
Hypothetically, it is possible for health-care facilities to quickly become epicenters if we are not vigilant about doing this. The same constellation of factors that gave rise to New York becoming the epicenter may exist in health-care facilities—dense populations with people coming from many different places using public transportation and extensive contacts among health-care workers and patients. Health-care workers are at high risk, and we must implement nasal and blood testing on a widespread basis.
We probably need to be able to conduct 1 million nasal and blood tests each daily in the United States during this and later high-risk COVID-19 periods to identify the spread of COVID-19 infection and trace/isolate contacts. We need to understand the prevalence and significance of COVID-19–neutralizing antibodies in relation to immunity once the infection has resolved. People who are immune can donate plasma to sick patients. We need to identify health-care workers who have become immune so they can be preferentially deployed at the forefront in the care of patients infected with COVID-19.
What is the approach to patients with leukemia being treated at your institution?
Of course, we emphasize the usual important measures—hygiene, handwashing, social distancing, no visitors for now—and we try to keep patients out of the hospital as much as possible. When they have low white blood cell counts, we try to protect them with antibiotics.
Small studies (from China and elsewhere) suggest that patients with cancer on active therapy or at the end of therapy may be more susceptible to mortality related to COVID-19. The study from China reported a mortality rate of 30+% among patients with cancer infected with COVID-19.
Managing Leukemias
How do you treat patients with acute myeloid leukemia (AML) during the COVID-19 pandemic?
All patients with AML who need intensive chemotherapy are tested for COVID-19 before starting treatment. If they test negative, we implement the treatment with intensive chemotherapy. In older patients and in those who are in complete remission, we may give them azacitidine plus venetoclax during high-risk COVID-19 periods.
Are you implementing any modifications for patients with acute lymphocytic leukemia (ALL)?
Treatment of ALL can result in lowering IgG levels. During the COVID-19 pandemic, COVID-19–neutralizing IgG needs to be produced to kill the virus and provide immunity. Patients with ALL and low IgG levels may be unable to mount an immune defense.
We are considering using less intensive therapy for ALL. At MD Anderson, we use mini-CVD (cyclophosphamide/vincristine/dexamethasone) in combination with inotuzumab ozogamicin/blinatumomab across the board in all adults with ALL if they are at high risk of developing COVID-19 infection. Also, COVID-19 is associated with disseminated intravascular coagulation and thrombosis. So, we avoid using asparaginase.
The University of Texas MD Anderson Cancer Center
What about treating patients with chronic lymphocytic leukemia (CLL)?
Patients with CLL may also have low levels of IgG. Many of these patients receive ibrutinib as standard of care. We are concerned that ibrutinib itself may influence complications if the patient has COVID-19, particularly pulmonary and cardiovascular adverse events. Some experts believe that ibrutinib may result in improving the cytokine-release syndrome related to COVID-19, hence a possible benefit with severe COVID-19 infections. Both ibrutinib and acalabrutinib are in phase III studies in patients with COVID-19.
How are you currently treating patients with chronic myeloid leukemia (CML)?
Depending on which therapy they are on, patients with CML could develop pulmonary problems, thrombotic events, and severe diarrhea. We hold therapy for patients who are on dasatinib and develop lung problems; for patients on nilotinib or ponatinib who develop vasospastic or thrombotic events; and for patients on bosutinib who develop severe diarrhea. In these patients, we pay particular attention to the respective side effects. If they develop COVID-19 infection, we stop the CML treatment until they recover.
Are you sending patients with CML to transplant?
We test for COVID-19 before sending patients for emergency transplant. If we can delay transplant, such as for patients with CML, we delay it.
Are there special considerations for patients with acute promyelocytic leukemia (APL)?
We do not make any modifications in managing patients with APL during this time. They are treated with all-trans retinoic acid and arsenic trioxide with or without gemtuzumab ozogamicin. These patients are not particularly immunosuppressed. One important caveat is never to use granulocyte colony-stimulating factor (G-CSF) growth factor support in a patient with APL. This is one type of leukemia where G-CSF can worsen the leukemia. All doctors who treat APL should be aware that, even if the counts are low, particularly during induction, never use G-CSF in these patients. This is a major red flag.
Blood Transfusion Support
During the COVID-19 era, have you modified the care of patients with AML who require long-term hospitalization for 3 or 4 weeks and blood transfusion support?
We do not test for COVID-19 in transfusion donors at present. Of course, any symptoms exclude donors, but perhaps donors should be tested with nasal and blood tests in the future, since 25% to 50% of patients with active COVID-19 may have no symptoms, as we do to exclude other infections. In published data, COVID-19 is reported to be present in the blood in just 1% of patients infected with COVID-19. We are not doing anything differently in terms of transfusion support.
Differentiation Syndrome and Coronavirus
Patients with AML and APL can present with symptoms of differentiation syndrome that mimic COVID-19 and require urgent intervention. How do you distinguish between differentiation syndrome and COVID-19?
This is not a big issue for us. We do not see it often in AML because we use chemotherapy with targeted therapies (FLT3 and IDH1/2 inhibitors). However, it is an important consideration for patients on treatment with checkpoint inhibitors, who can develop pneumonitis, nephritis, hepatitis, and other inflammatory conditions and are treated with steroids. COVID-19 testing helps in these situations, testing both with nasal swabs (active infection) and blood. We can combine the test results with early IgM levels to improve the detection capacity for active COVID-19 infection. Computed tomography (CT) of the chest in such cases may help distinguish COVID-19 changes from others.
Rapid COVID-19 testing is needed for patients with leukemia or solid tumors on checkpoint inhibitors when the side effects of these drugs may be similar to those of COVID-19. This is also true for patients on chimeric antigen receptor T-cell therapy.
Nasal Test for Coronavirus
Is the nasal COVID-19 test sensitive enough and specific enough to detect infection?
The nasal test can detect 60% to 70% of patients with COVID-19 infection. If the test is done twice, this may reduce false-negative results to under 15%. It is also important to do a CT scan of the chest to identify COVID-19–suggestive changes in patients who test negative but have symptoms suggestive of COVID-19. The CT scan provides sometimes important findings suggestive of COVID-19 infection, and we are starting to do CT of the chest when we suspect COVID-19 but the nasal swab is negative.
DISCLOSURE: Dr. Kantarjian has received honoraria from AbbVie, Actinium, Agios, Amgen, Ariad, Bristol-Myers Squibb, Immunogen, Orsenix, Pfizer, and Takeda; and has received institutional research funding from AbbVie, Agios, Amgen, Ariad, Astex Pharmaceuticals, Bristol-Myers Squibb, Cyclacel, Immunogen, Jazz Pharmaceuticals, Novartis, and Pfizer.
