May 7, 2020

As the COVID-19 crisis enters a new phase of re-opening in some places, it is important to assess what the new abnormal is going to look like. Within this new abnormal it is essential to achieve the best myeloma care possible. So, let’s start with myeloma care for 2020 and then review the impact of COVID-19.

Myeloma Care 2020

• Annual clinical update: IMF Board of Directors member and co-chair of the International Myeloma Working Group (https://www.myeloma.org/international-myeloma-working-group) (IMWG) Vincent Rajkumar, MD, has just published his 2020 Update on Diagnosis, Risk-Stratification and Management (https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25791). As always, Dr. Rajkumar presents his personal perspective while referencing all the most current published data. All in all, an excellent overview! Helpful information includes:

  • The full diagnostic criteria, which is important since there are many details that change year-to-year.
  • Updated risk-stratification, which now includes important factors such as abnormalities of chromosome 1 and the concepts of double-hit and triple-hit disease, in which patients have multiple high-risk FiSH test or molecular abnormalities.
  • Drugs and dosages/schedules for all the commonly used treatments.
  • Summary treatment algorithms for frontline therapy and relapse.
  • Comments about the newer agents, such as Ixazomib, Selinexor and Isatuximab.
  • However, only brief mention of the emerging anti-BCMA immune-therapy options of CAR T-cell therapy, antibody-drug conjugate (belantamab) and bispecific T-cell engagers.

• New Approvals:

  • Daratumumab (Darzalex) has just been approved by the FDA (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-daratumumab-and-hyaluronidase-fihj-multiple-myeloma)for subcutaneous injection (Darzalex Faspro) versus the prior intravenous-infusion-only administration. This is an important step forward, both for convenience and tolerance, and will make both induction and maintenance schedules much more manageable, especially in this era of COVID-19 infection.
  • Isatuximab (Sarclisa), an alternate anti-CD38 monoclonal antibody, was also recently approved by the FDA (https://www.fda.gov/drugs/development-approval-process-drugs/fda-approves-isatuximab-irfc-multiple-myeloma) for use in combination with pomalidomide and dexamethasone in patients with prior exposure to lenalidomide (Revlimid) and a proteasome inhibitor, such as bortezomib (Velcade), carfilzomib (Kyprolis) or ixazomib (Ninlaro). It is great to have another option available in that setting.
  • Anticipated FDA approvals include those for the anti-BCMA-drug conjugate (belantamab) and CAR T-therapies.

• COVID-19-specific suggestions: We are fortunate that several myeloma experts have provided guidance from experience on the frontlines treating patients during this health crisis. Among them is Dr. Suzanne Lentzsch of New York Presbyterian Hospital/Columbia University Medical Center in New York City. Writing in Clinical Care Options (https://www.clinicaloptions.com/oncology/programs/myeloma-treatment-strategies/clinicalthought/ct4/page-1), Dr. Lentzsch estimates that 20% of the patients in her practice have been COVID-19-infected. This reflects the high risk of contracting COVID-19 in New York City. Many were asymptomatic, and although a few required hospitalizations, none died and all are on the course to recovery. The guidelines she is currently following include:

  • Requiring two negative COVID-19 tests BEFORE patients can come to the outpatient clinic. Obviously, alternate strategies may emerge as risks drop and /or if for example antibody tests become more reliable.
  • Several treatment modifications to consider:
    • Using oral options as much as possible, such as Ninlaro, an oral proteasome inhibitor, versus Velcade or Kyprolis.
    • Holding or delaying IV bisphosphonate therapy (Zometa or Aredia).
    • Carefully reviewing the risks of possible infections in patients taking Darzalex.
    • Delaying invasive therapies such as ASCT (autologous stem-cell transplant).
    • Replacing in-person visits with telemedicine is recommended to limit the need for clinic visits. This will continue moving forward as an alternate approach for routine care.

Accessing the best care in 2020 and 2021

This past week there have been several important perspectives published on what the new abnormal will look like:

• Laurie Garrett on what is needed now: A broad perspective comes from the author of the 2017 book, “Warnings: Finding Cassandras to Stop Catastrophes” (https://www.nytimes.com/2020/05/02/opinion/sunday/coronavirus-prediction-laurie-garrett.html) and the 1994 bestseller, “The Coming Plague: Newly Emerging Diseases in a World Out of Balance.” (https://www.lauriegarrett.com/the-coming-plague)She feels very strongly that America needs to know:
  • How many people in your community have been exposed to COVID-19?
  • Where have any new infections come from?
  • What are the true risk factors for developing a new infection?

  With this information, everyone can gauge the risks of venturing out as our society reopens and if, for example, a myeloma patient decides to venture back to the myeloma clinic or the grocery store.

  BOTTOM LINE: In the absence of this information, which is the current situation, myeloma patients must continue stay home for safety or venture out only with due cautions and physical distancing.

• Bill Gates on breakthroughs emerging from the pandemic: Writing in The Economist (https://www.economist.com/by-invitation/2020/04/23/bill-gates-on-how-to-fight-future-pandemics) magazine, Bill Gates describes three big medical breakthroughs that will be hastened by the coronavirus:
  • Vaccines: using the messenger-RNA approach to speed vaccine development. This is the approach taken by the Oxford University research team (https://www.popsci.com/story/health/covid-19-vaccine-oxford-september/).
  • Home diagnostics for COVID-19 (or other pathogens) diagnostic testing: providing rapid, easy results globally.
  • Good anti-viral therapy: possibly in the form of a multi-drug “cocktail” as used for HIV/AIDS.

  These important innovations will be transformative but will take some time.

New information that can help right now?

• Testing of communities: Recent testing in a German town after it hosted a local festival indicated that 14% of the townspeople had been COVID-19 exposed (https://www.dw.com/en/18-million-people-in-germany-could-be-infected-with-coronavirus-researchers-find/a-53330608). This number of cases posed a challenge for the town in providing medical care but resulted in an extra buffer of immunity should new cases emerge. It represents a dilemma faced by so many communities: take risks that can impact the most vulnerable or not? Much broader testing and contact tracing are required to produce this type of information.

• Role of antibody tests: Antibody tests can indicate exposure to COVID-19, but unfortunately, do not necessarily indicate immunity. Thus, the tests can help track the spread of COVID-19 in the community but cannot yet be used on an individual basis to allow safe entry into the social or work environment. Physical distancing and masks are still required in public settings. Better antibody tests are on the way. Of note this week:

  • The FDA just approved (https://www.cbsnews.com/news/roche-coronavirus-antibody-test-fda-approval-accuracy/) a new Roche antibody test method.
  • Interesting new research with llamas (https://www.nytimes.com/2020/05/06/science/llama-coronavirus-antibodies.html) indicating that they could become coronavirus heroes. Small llama antibodies can detect the key spike protein of COVID-19 better than larger human antibodies. These animal antibodies can be fused with human equivalents and perhaps be used for both testing and treatment. One never knows which research will turn out to be transformative!

• Wastewater analysis for covid-19: A unique way to study how many patients are still infected in a community is to test the sewage or wastewater coming from a community. (https://www.wsj.com/articles/in-sewage-scientists-find-not-just-waste-but-coronavirus-clues-11588762803?redirect=amp#click=https://t.co/XE5uNBEdqR) Around the world this method is now being used to detect early shifts in negative versus positive and/or the amount of COVID-19 in the wastewater. Obviously, a negative finding would strongly support lifting of a lockdown in a particular region.

• Using dogs to sniff it out: Another non-invasive way to assess COVID-19-positivity is a project training dogs to detect COVID-19 carriers who are asymptomatic (https://www.washingtonpost.com/science/2020/04/29/coronavirus-detection-dogs/). Hopefully, their training will be finished soon.

• Studying new covid-19 mutations: A remarkable paper (https://www.biorxiv.org/content/10.1101/2020.04.29.069054v1?versioned=true) published by the research team at the Los Alamos National Laboratory indicates that the now-dominant strain of COVID-19 (different than the original strain) appears to be more contagious/infectious than the strain first found in Wuhan, China. The spike protein of COVID-19, which binds to the surface of cells to gain entry, has mutated to a form which leads to a much larger amount of virus (a higher viral load) in patients, and higher infectivity.

  This new strain became dominant in Europe starting in Germany, then in Italy and Austria. It was then transmitted to New York and possibly back to China. This strain has become dominant in all countries and appears to account for the more dangerous consequences evident in places like Italy and New York.

  The ongoing molecular-sequencing project, which was released as rapidly as possible to make sure this new strain is included in global vaccine efforts, will track mutations and provide timely alerts as changes emerge.

The need for global collaboration

The identification by researchers at the Los Alamos National Laboratory of new mutations in the COVID-19 spike protein illustrates what can be achieved using open platforms and maximizing input from groups with different areas of expertise. Each group in this study worked in parallel, rather than waiting for all other results to become available, and none were duplicating efforts. If this sounds familiar, it is exactly the way the IMF Black Swan Research Initiative (https://www.myeloma.org/black-swan-research-initiative)works in the search for prevention of and a cure for multiple myeloma. It is also what we need right now to achieve the best COVID-19 testing, screening and contact tracing, to develop the best vaccine and to develop the best new antivirals. Such public-private collaborations are, fortunately, already happening in informal ways. But true, coordinated efforts, multiple mini-Manhattan projects, would be a welcome development.

Staying resilient despite uncertainties

As we work through the details of this new abnormal, it is encouraging that the promise of many new innovations will help us get through this evolving period together. Not surprisingly, our eating patterns are changing. Grocery stores have noted a dramatic increase in orange juice sales, which, I guess, we all think may help fight off the virus. Another sold-out item is frozen pizza, which is a panic buy for emergencies or perhaps convenience. A fun new book, “Ingredients: The Strange Chemistry of What We Put in Us and on Us,” (https://www.amazon.com/Ingredients-Strange-Chemistry-What-Put/dp/1524744271) by George Zaidan, looks at the ingredients in processed foods, which you might want to read (or not) before consuming too much of the stuff.

A book I recommend to overcome quarantine fatigue is “Talking with Bears,” (https://www.amazon.com/Talking-Bears-Conversations-Charlie-Russell/dp/1771603615) by G. A. Bradshaw. This heartwarming book, highlighting conversations with the naturalist Charlie Russell (https://en.wikipedia.org/wiki/Charlie_Russell_(naturalist)), is “a treasure of inspiration for those who hear the whispering calls of nature and yearn for more connection.”

So, as we end another week of our new abnormal, let’s focus on what can give us strength and renewal for this adaption to a new future for all of us.

Translations:

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