July 2, 2020

As we watch COVID-19 cases spiral out of control across the U.S., there is an emergency reality check: how do we stop this? How do we flatten this dangerous upward curve? Some political leaders in the most seriously affected regions have only now begun a reluctant pivot toward science for answers. Fortunately, science can help produce evidence-based practices and can guide the country towards strategies that will reduce this pandemic, allow a sensible reopening, and help us achieve the best outcomes for patients with myeloma.

Science and Myeloma Patients 

• COVID-19 risks

It has been a struggle to understand the exact risks COVID-19 poses to myeloma patients. A recent paper from the Spanish Myeloma Collaborative Group network provides very helpful information. The study of 167 myeloma patients admitted to the hospital for COVID-19 infection compared outcomes to a matched population (categorized by age, sex, and those without cancer). This allowed the impact of having myeloma or not to be clearly assessed. The overall mortality rate for patients without myeloma was 23%. The overall mortality for patients with myeloma was 34%. There was an approximate 10% increased risk for patients with myeloma. For myeloma patients, the factors associated with further increased risk were: men (versus women); age greater than 65 years; currently active or progressive myeloma (newly diagnosed or relapsed); and chronic kidney issues. This is extremely helpful information in assessing risk for individual patients.

• Ongoing research, including the Black Swan Research Initiative: 
  • Despite the impact of COVID-19, research in the laboratory and the clinic continues. While there were significant shutdowns for several weeks, most research is back up and running and can continue with appropriate safety precautions in place. A new report illustrates the value of monitoring myeloma using blood testing. This is a major step forward to avoid repeated bone-marrow testing for assessment of minimal residual disease (MRD). The presence or absence of myeloma plasma cells in the blood and the numbers of such cells indicate the likelihood of sustained MRD negativity (and the potential for cure) versus a potential for early relapse.
  • Laboratories and clinical trial programs around the world are reopening and await results on many important studies. For the IMF’s Black Swan Research project, we are especially interested to see new data about MRD and ongoing results with both the CESAR and ASCENT CURE trials. It will be possible to have an abstract presented at the American Society of Hematology (ASH) meeting this year to summarize the initial findings in the ASCENT trial, which is the U.S. trial incorporating Darzalex, Kyprolis, Revlimid and dexamethasone in the treatment of high-risk smoldering myeloma (HR-SMM). Results are very encouraging, with high levels of deep response being achieved.
  • The details of the new scoring system being used to diagnose HR-SMM (previously presented at ASH and American Society of Clinical Oncology meetings) have been submitted for publication and, hopefully, will be accepted for early release. This builds on the 2/20/20 system in which the cutoff values of 2 GMs/dL for the serum monoclonal protein level; 20 for the Freelite ratio; and 20% for the percentage of plasma cells in the bone marrow are used to identify patients with high-risk disease. This system will help us precisely document HR-SMM as a basis for early and potentially curative intervention.

The bottom line: Active research continues to help myeloma patients.

Science and Preventing the Spread of COVID-19 

• QUESTION #1: Who are the super spreaders?  

A recent New York Times article summarizes the science related to super spreaders. The first step in understanding super spreaders is to know that when COVID-19 first arrived in Italy from China in December 2019, as indicated from wastewater samples in Milan and Turin, there was no major surge of COVID-19 infections until about two months later.

There was ongoing asymptomatic community spread before the sudden super spreader event in late February 2020. For reasons still not understood, COVID-19 multiplies to much higher levels in some individuals. Ultimately, infection occurred in such a  favorable super-spreader “host.” 

These hosts can be asymptomatic about half the time, and one infected individual can spread the virus to 20 or more people. This process also leads to an opportunity for new strains or mutations to emerge. The one that emerged in Italy is the D614G mutation, which is a much more infectious COVID-19 strain than the original Wuhan virus. 

• Action steps:
  • Further research is required to better understand super spreaders. 
  • Community monitoring is necessary to detect ongoing community spread and assess the level. In Italy, wastewater-testing revealed the situation in retrospect. It is now proposed that prospective pooled testing of multiple swab samples can be used to screen a community. If the percentage of positive tests is rising, a problem is detected before a full surge occurs. 
  • Intervention to test and trace at a level when there is an opportunity to quarantine and contain further spread and limit the chance of a super-spreader event.
  • If feasible, collaborate with consortia studying COVID-19 mutations and strains to see if any new strain has emerged in the local community. If there has been a dramatic surge in case numbers, this may indicate that a new strain is present.

• QUESTION #2: When does the spread occur? 

It is important to identify super spreaders, those who develop a high viral load and spread much more virus into the air, as early as possible. There is a window of time—starting a couple days after infection, but before symptoms emerge, until a variable time after symptoms begin (two to three weeks)—when high-level spread occurs. This means that early testing and tracing are crucially important to document the one individual who has the capacity to spread to multiple others. Rapid-turnaround testing is key. But, according to one report, one-day testing is a growing challenge as the country’s largest medical-testing companies face overwhelming demand.

• Action steps: 
  • Be aware that asymptomatic spread can lead to a super-spreader event and can be a source of infection for every individual entering the community.
  • Put in place a testing, tracing, isolation protocol that can allow for early intervention. It is perhaps reassuring to know that even in Iceland a couple of cases of COVID-19 cropped up this past week. Ongoing vigilance is essential. In the U.S., unfortunately, we have a long, long way to go to get to this low-level monitoring and vigilance stage. 
  • Mandate masks, physical distancing, and stringent public health measures to limit exposure events and person-to-person spread.

• QUESTION #3: Where does the spread occur? 

This is the crucial element of COVID-19 spread. If a super spreader is in a large group setting, especially indoors, incredible spread can occur fast. These situations are now well documented and include bars, restaurants, churches, workplaces, nursing homes, day care centers, weddings, funerals, concerts, and karaoke parties, to name a few. Even beyond larger venues, other meetings and contacts must be closely guarded. If a super spreader is in a small group, the spread will be limited and there will be an opportunity to test and trace effectively. The strategy of implementing small “bubble groups” (less than 10 in the group) has been evaluated in day care centers and it has worked well to avoid broad exposures.

•  Action steps:
  • Eliminate group gatherings! Some have said that just eliminating large group gatherings would control COVID-19 spread. I agree that it would truly blunt the super-spreader effect and allow interventions to occur. Limit or carefully construct even smaller group gatherings.

Science About COVID-19 Disease 

A recent report summarizes the unusual effects of COVID-19 infection—the occurrence of many small blood clots in the lungs, brain and other organs and tissues. Organ and tissue damage are occurring not because of direct virus invasion, but due to the triggering of blood clot formation involving blood platelets. Even the cells that produce platelets, called megakaryocytes, which are normally found only in the bone marrow, have been noted in damaged lungs. Blood clots reduce blood flow and deprive cells of oxygen. There is concern that this type of damage can lead to a permanent injury, especially in the case of heart, kidney, and brain tissues, in addition to the lungs, which are the primary target of COVID-19.

• Action steps: 
  • Further research is required. 
  • Blood thinners, such as anti-platelet agents like aspirin, need to be further evaluated and could improve outcomes. However, all types of blood thinners must be used with caution in patients with myeloma. 

The Benefit of Science

Our growing understanding of the science of COVID-19 can inform day-to-day decision-making as we head into the challenging months ahead. Already, the heroic healthcare workers and first responder teams are under severe stress in Texas, Arizona, California, and Florida.

But beyond this surge, the control of COVID-19 is absolutely feasible through good planning and the use of technology until a decisive anti-virus therapy or a vaccine is available. For now, it is essential to stay safe at home and limit opportunities for virus exposure. Please keep this in mind over the Fourth of July weekend. This would be a good year to avoid the crowds and enjoy fireworks on TV.

Dark clouds can always have a silver lining, so I leave you with beautiful images of clouds by Denmark-based artist Morten Lasskogen to allow you to step away and build your resilience, which may be depleted and in need of a boost. Please stay safe and healthy!

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Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.