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Director, Multiple Myeloma and Amyloidosis Program
Professor of Medicine
Division of Hematology/Oncology
Columbia University Medical Center
New York, New York
In this commentary, I discuss my experiences with how I am managing my patients with multiple myeloma (MM) during the COVID-19 pandemic. First of all, it is important to point out that this situation differs from location to location and what might be the best approach in New York City, where I am seeing patients, might not be the best approach in other cities in the United States or in other countries around the world. Here in New York City, people have a higher risk of contracting COVID-19, and in particular, the probability of being infected with SARS-CoV-2 (the virus that causes COVID‑19) when coming to the hospital is higher than other areas in the United States.
Treatment Considerations in High-Risk Areas
Due to the higher risk of infection when traveling to the hospital in New York City for infusions, we switched treatment regimens for MM to oral medications as much as possible or recommended delaying or holding therapy. Thankfully, we have several oral treatment alternatives for patients who need to remain on therapy. For instance, patients receiving bortezomib/lenalidomide/dexamethasone can use ixazomib as a weekly pill in place of bortezomib and continue treatment with an all-oral regimen.
Patients who were on medications requiring IV or SC administration—like daratumumab, bortezomib, or carfilzomib—and who could delay or hold therapy for several weeks are holding treatment to avoid the need to come to the hospital. For patients who have already achieved remission and are on continuous therapy to achieve a deeper response (eg, for minimal residual disease negativity) or for those on IV or SC maintenance therapy, we are also holding therapy. In addition, we are holding supportive care such as bisphosphates, denosumab, and IVIG therapy for some patients. The interval of denosumab or bisphosphonates administration can also be increased to every 3 months in patients without urgent problems such as hypercalcemia.
These approaches are recommended in areas with widespread SARS-CoV-2 infections with very high risk of coming in contact with infected people. Using these policies, we have been able to avoid having most patients come into the hospital and many patients were able to stay home safely.
Treatment Considerations in Lower-Risk Areas
If you are in an area that has been less affected by COVID-19 and you have access to SARS-CoV-2 tests for staff and patients, you may be able to continue treatment regimens that require the patient come in to the clinic for administration. For instance, as rapid SARS-CoV-2 testing becomes available, these tests could be used by patients the day before their appointment to confirm SARS-CoV-2 negativity before coming into the clinic. However, the availability and turnaround time of testing poses a logistical challenge that needs to be addressed before this can be broadly implemented.
When considering which MM treatment regimens to use, for patients who do not have COVID-19, clinicians should balance the risks and benefits for individual patients based on their specific situation. For example, for a patient with newly diagnosed high-risk MM who initially presented with hypercalcemia, the risk of rapid progression may outweigh the risk of coming into clinic for treatment, and IV-based therapy should be recommended. In selected cases when patients need more intense care that would require frequent visits to an outpatient clinic, such as for hypercalcemia, hyperviscosity, pain, or radiation therapy, we prefer admission to our COVID‑19–free floors in the hospital to avoid frequent travel. We think that it is safer to keep a patient in the hospital for 3-5 days for treatment than to have a patient traveling several times to the hospital and having multiple interactions with other patients and staff or be potentially exposed to the virus on public transportation.
Should ASCT Be Held?
This is a common question right now that each center needs to consider. In New York, we have placed all MM autologous stem cell transplants on hold. Based on current data, we think that continuing with additional cycles of induction therapy with a proteasome inhibitor/immunomodulatory drug (IMiD)–based combination is acceptable to bridge to ASCT once it is available.
The main reason why we are not recommending ASCT at the current time is not so much that we are concerned about patients coming into the hospital and becoming infected during their stay but more so a matter of making sure resources in the hospital setting are available for additional support if required.
Patients should continue with stem cell mobilization with appropriate precautions (eg, PPE for clinicians and patients), and ASCT can be scheduled after this COVID-19 pandemic has abated.
In a few instances, we may consider administration of CAR T‑cells for life‑threatening diseases, such as acute leukemia, diffuse large B‑cell lymphoma, or patients with advanced or aggressive MM.
Considerations for Specific Treatment Options
In addition to the treatment considerations I have mentioned above, there are some additional concerns when selecting MM therapy. In general, for any patient with cancer during the COVID-19 pandemic, clinicians should consider if a treatment could result in a decreased immune response. In MM, daratumumab is associated with an increased risk of severe infection due to inadequate antibody response and inhibition of antibody-producing plasma cells. Based on this potential decreased immune response and antibody production, I am holding daratumumab therapy and reassessing the risk and benefits of therapy for patients weekly.
Conversely, we have some anecdotal data that the XPO1 inhibitor selinexor and proteasome inhibitors might be of benefit to control COVID-19. There are also conflicting perspectives with IMiDs: On the one hand, they might worsen COVID-19 due to an increase in T-cell activity contributing to lung inflammation, but on the other hand, IMiDs may inhibit cytokine production, resulting in potential reduction of inflammation. We need more data to confirm these anecdotal findings, and trials are ongoing. In addition, many organizations such as ASH, ASCO, the International Myeloma Society (IMS), and the Multiple Myeloma Research Foundation (MMRF) are collecting data that might provide more information on how specific MM treatments affect COVID-19 outcome.
Monitoring for Disease Response or Progression: Telemedicine Approaches
Once we have determined the optimal treatment approach for our patients with MM, the next hurdle is monitoring patients for response or progression. In New York, we have been transitioning to telemedicine appointments and are asking our patients with MM to go to a local laboratory to have blood drawn for response assessment. For our sickest patients, our older patients, and those who should not take the risk to even go to a local laboratory, we are arranging blood draws at the patients’ homes.
Telemedicine visits are different than in-person appointments with physical exams, and clinicians need to find ways of assembling missing information. For example, I ask my patients, “Can you please take your blood pressure? Can you please give me your latest weight?” to obtain vital signs and information via telemedicine. Clinicians can also make a visual assessment and ask for the patient to show any abnormalities like any rashes or lower extremity edema. As good as telemedicine is, I think it covers approximately 60% to 70% of the information you can obtain in an in-person visit. Clinicians may miss critical information such as how the patient walks into the room or his or her ability to get on the exam table. Therefore, I do not think that telemedicine is really the best way to treat patients with MM, but it is the best way to treat patients right now during the pandemic.
Testing for COVID‑19
As I mentioned above, the only way to ensure that your patient is COVID-19 free is through repeat testing. People who are infected with SARS-CoV-2 can have a period of up to 2 weeks with no symptoms prior to developing symptoms of COVID-19 or can be oligosymptomatic or asymptomatic throughout the entire course of their disease. Therefore, SARS-CoV-2 testing and thorough assessments of potential COVID-19 symptoms before starting patients on MM therapy are essential.
Unfortunately, there are no guidelines for how often and when to test patients with cancer for SARS-CoV-2. We currently require 2 negative SARS-CoV-2 tests before patients can come to the outpatient clinic and restart treatment. Patients currently receiving MM treatment might need weekly testing and patients who experience any new or worsening shortness of breath or fever also require testing. Unfortunately, in many hospitals, frequency of testing for SARS-CoV-2 is dictated by the availability of testing. I would also encourage clinicians to remind their patients that social/physical distancing is the best prophylaxis to avoid COVID-19.
SARS-CoV-2 is an interesting infection because we see so many different presentations ranging from having no symptoms or just a loss of smell and taste to severe cough or transitioning to devastating cases with acute respiratory distress syndrome (ARDS) and respiratory failure. I estimate that 20% of my patients with MM have been infected. Given how immunocompromised many of our patients with MM are and the potential for an inadequate immune response for patients on MM therapy, clinicians should try to minimize the potential for their patients to contract COVID-19 through patient education, testing, minimizing patient travel and contact, and using appropriate PPE when in-person visits are necessary.
How are you managing your patients with MM during the COVID-19 pandemic? What are your biggest concerns? I encourage you to answer the polling question and join the conversation in the discussion box below.
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