Charting New Territory in Multiple Myeloma Amid COVID-19 Crisis

Ajai Chari, MD

The severity of the novel coronavirus 2019 (COVID-19) is heightened among patients with cancer, particularly patients with multiple myeloma who have decreased immunity by nature of the disease, said Ajai Chari, MD. However, the use of personal protective equipment (PPE), delaying elective procedures, and converting patients in need of therapy to oral-based regimens can help reduce the spread of the virus and protect those at greater risk.

“We’ve eliminated all elective procedures, including transplant collection, stem cell collection, stem cell transplant, clinical trials, as well as bone marrow biopsies and imaging procedures—–anything that's not required to take care of the patient is being postponed,” said Chari. “If a patient doesn’t have very low blood counts or complicated chemistry, we're trying to avoid laboratory testing. If those patients don’t have to have injection-based therapy, we are switching to oral-based regimens.”

In an interview with OncLive, Chari, an associate professor of hematology and medical oncology at Mount Sinai Hospital, discussed the impact of the COVID-19 outbreak on hospital protocols and the measures that are being taken to reduce the spread of the virus.

OncLive: What do we know about the risk of COVID-19 to patients with cancer?

Chari: We have very limited data, but 1 of the publications in Lancet Oncology, by Wenhua Liang et al, showed that patients with cancer have a higher complication rate [from COVID-19]. Thirty-nine percent of patients with cancer had severe events, including a stay in the intensive care unit, ventilation, or death versus 8% without cancer. [That rate] seemed to be even higher in patients who had recent chemotherapy or surgery. Older patients with cancer seem to have a higher rate of complications. For these reasons, we really need to think about the time point each patient with cancer is at in their disease continuum. We need to think about the risks and benefits of [coming to the cancer center] for each individual patient with respect to the risk of leaving their home. We also have to think about the risk of nosocomial infection because the other patients have caregivers. We always say that hospitals are not a good place to be if you don't need to be there, especially now in the COVID-19 era.

Should patients wear PPE if they have to go out?

Because of the vulnerable nature of our patients with myeloma, it's probably a good idea [that they wear PPE]. We recommend that everyone self-isolate and follow [organizational] guidelines, but myeloma patients in particular are a vulnerable population. The median age of patients with myeloma is in the 60s and 70s. Patients also have, by the nature of their disease, decreased immunity because their plasma cells aren't making enough antibodies. Patients have impaired humoral immunity, which results in less antibody production. Infections are a very frequent cause of morbidity and mortality in myeloma, independent of COVID-19. Finally, chemotherapy may also contribute to the risk of infection. We don’t have great guidelines, so I would say at least a surgical mask, and frequent hand washing and [use of] gloves is not unreasonable.

How are healthcare providers dealing with the shortages of PPE?

There is a nationwide shortage of PPE, but a lot of efforts are being put into that.

Could you discuss the steps that are being taken to safeguard patients and providers?

Most facilities are putting very strict screening and visitation policies in place. At our cancer center, visitors are not allowed [in] because that extra person means extra risk. Visitors are not being allowed into cancer centers or in most hospitals, including for example in labor and delivery. Many hospitals are restricting women who are about to deliver from having a visitor.

We’re also screening patients as soon as they enter the building to further minimize the risk [of community spread]. Do they have upper respiratory infection symptoms? Do they have a fever? Have they had contact with someone who tested positive for COVID-19? If any of those things are true, they go to a specific room. The staff that enter will be wearing a surgical mask and gloves at minimum. Depending on the situation, they may need to wear the full gown and [use] additional protective equipment if COVID-19 testing is deemed necessary.

Has the outbreak impacted the use of CAR T-cell therapy?

CAR T-cell therapy is not yet FDA approved in myeloma. As of almost a week and half ago, we have halted all clinical trial accrual, so we’re not enrolling any new patients on trial. The only patients that are getting research-related therapies are those that have already started the treatment.

Is bridging therapy being used longer to delay the need for stem cell transplant?

One of the complexities of dealing with COVID-19 with respect to myeloma is some of our treatments. For example, CAR T-cell therapy and bispecific drugs can be associated with fevers and cytokine release syndrome (CRS). COVID-19 can also produce CRS. If a patient is receiving [1 of these] therapies and develops a fever, it's going to be potentially difficult to tell whether it's related to the drug or due to COVID-19 infection. That’s 1 of the things we're trying to avoid. [The same is true] in a patient who has undergone a transplant. If these patients have low white counts and develop a fever, is it a regular fever that posttransplant patients get, or is a COVID-19-related fever?

COVID-19 is a serious illness in [the general population], let alone in patients who have no immune system. Patients who are neutropenic and have low blood counts have an even further suppressed immune system compared with the typical patient. It's not prudent to undergo [those treatments], so we’ve stopped all new research activity. A lot of inpatients on existing studies are getting intravenous (IV) or subcutaneous therapy. We're potentially skipping some doses in patients if we think their disease is well controlled. We've also halted all elective procedures, including stem cell collections, stem cell transplant, and clinical trials. We’re not planning to do anything that is not required right now.

How are you approaching treatment decisions for patients on active therapy?

It's a question of the risk-benefit ratio which can change not only for a particular patient at a particular time, but also where we are in the [lifespan of COVID-19]. Our approach 3 weeks ago versus this week versus two weeks from now is going to change because of the rapidly evolving nature of the disease. Our guidelines need to be commensurate with the risk [at that time]. Newly diagnosed patients or patients whose disease has progressed—–the patients we’re more worried about, don’t have the luxury of delaying therapy.

Luckily in myeloma, we have oral regimens for a lot of different drug classes. We have oral steroids, oral proteasome inhibitors, such as ixazomib (Ninlaro), and oral immunomodulatory drugs, such as thalidomide, lenalidomide (Revlimid), and pomalidomide (Pomalyst). The alkylating drugs like cyclophosphamide and melphalan are oral, so we have a lot of oral drugs to play with. We also have panobinostat (Farydak) and selinexor (Xpovio), so depending on what a patient needs, we can come up with a good oral regimen. If the side effects of a particular cocktail are going to require very intensive laboratory monitoring, that may not be the ideal cocktail. We’re trying to make very well tolerated oral regimens that don't require frequent monitoring.

For patients in remission, we're skipping subcutaneous and IV injection until COVID-19 resolves, and if needed, continue them on oral medications alone. But again, patients in remission may be able to skip that. Those patients are also getting IV immunoglobulin, which is a way to prevent recurrent infections. If a patient has had recurrent bacterial infections, we’re continuing that. These protective antibodies can last in the system for several weeks. If [IV immunoglobulin isn’t] absolutely indicated, on a case by case basis, we may skip a dose or two as well. Those are some of the things we're doing with treatments. The other things we're also trying to do is avoid, if at all possible, having patients come in for lab tests. We're looking at other ways of getting lab draws done.

What considerations should be made for patients switching to oral-based therapies?

It's important to remember that we're not monitoring these patients in person. We are moving to video visits and telephone visits, which is great, but that still can limit us from doing vital signs and laboratory [test]. For those patients on home steroids, like dexamethasone, we're reminding them to check their temperature in the morning before taking the drug because it can suppress fevers. If somebody was having some vague symptoms, and they took dexamethasone, it could mask their fever for up to two to three days. So we definitely want people to check their temperature and call us if they have any respiratory symptoms, fevers, or known COVID-19 exposure because even if somebody feels well, and they're on an oral chemotherapy regimen, we may want them to hold their chemotherapy entirely for at least one week to make sure that if they've been exposed to somebody with COVID-10, unknowingly or knowingly, we're not continuing chemotherapy without monitoring that patient for at least one week to make sure they don't develop any new symptoms.

These are complicated chemotherapy regimens. When our nurses were outstanding, and our physicians were working closely with our nursing team to switch patients over to these oral regimens, we always encourage patients to have a family member present at the iPhone or iPad, so that they can hear what changes are being made. If there's any uncertainty [regarding what to do] once these pills which are being delivered to the patient arrive, we ask them to call us. Some of these drugs, for example, are given once a week, some of them are given daily, some of them are given three weeks on one week off. All this complexity can be a little overwhelming, and it can lead to dosing errors. If a drug is supposed to be taken once a week, and somebody takes it three days in a row, that could be a big problem. So, we'd rather have patients call.

We're also prescribing supportive care. If we know there's the possibility of nausea from a medication, we're prescribing anti-nausea drugs, so the patient already has it ready to go rather than having to scramble to try to get drugs at the last minute. Those are some of the things we're doing to try to help with this transition to oral medications.

Lastly, if somebody needs to come to a medical center emergently, we're trying to engage our social workers to help with transportation. Many patients do drive, which is good. However, for patients who may have disabilities or don't have a car, our social workers are available to help with transportation. Social workers can also help [with finances]. Some of these oral chemotherapy drugs can be associated with copays. Fortunately, a lot of pharmaceutical companies have patient assistance programs. Hopefully, those assistance programs and our social workers can help decrease some of the financial cost of these oral therapies.

Should providers discuss code status with their patients during the pandemic?

While there are very exciting research studies ongoing for medical therapy, [such as] infusion of plasma from convalescent individuals, and infusion of mesenchymal stem cells for those with acute respiratory distress syndrome, it may not be unreasonable to discuss advance directives with patients.