October 29, 2020

As a lifelong scientist, I rely on and trust the results of gifted and honest researchers. I also strongly believe in the power of new research, information, and results. That is why I am grateful for the research funding generated by the recent and highly successful IMF Virtual Comedy Celebratio (https://www.myeloma.org/14th-annual-imf-virtual-comedy-celebration)n. The support helps us constantly move forward on all fronts in treating myeloma and finding a cure.

In recent science news:

A new risk stratification for smoldering myeloma

This past week, a landmark paper (https://www.myeloma.org/imwg-new-risk-stratification-model-for-smoldering-multiple-myeloma) from the International Myeloma Working Group (IMWG (https://www.myeloma.org/international-myeloma-working-group)) outlined a new system to identify patients with smoldering multiple myeloma (SMM) at a high risk of progressing to active myeloma within the coming months. The system relies on the levels of three factors:

1. M-protein level in the blood (more than 2G/dL)
2. Percentage of plasma cells in the bone marrow (BMPCs of more than 20%)
3. Ratio of involved over uninvolved serum Freelite levels (more than 20)

From an analysis of over 2,000 patients recruited from 75 centers globally the results have been scientifically validated, resulting in a critically appraised consensus guideline. Why is this new IMWG risk stratification model so important for myeloma patients and doctors?

The new model:

• Offers optimal early intervention
  This model allows us to build on years of research indicating that the earlier treatment is started, the better the outcomes. The key has been to avoid treatment for patients with early disease who are NOT at risk of progressing to active myeloma. This new risk system allows us to reliably offer treatment in this very early disease setting in hopes of achieving the optimal results. We have learned from randomized trials (with half of the patients being observed and the other 50% receiving active treatment) that outcomes are definitely improved. Now, from the CESAR (https://www.myeloma.org/videos/curative-strategy-gem-cesar-high-risk-smoldering-myeloma-smm) and ASCENT (https://www.myeloma.org/black-swan-research-initiative/black-swan-research-projects) trials (single-arm trials in which all patients are treated), outcomes are being even further improved with the use of the best new combinations as a first step.
• Builds a knowledge base
  The new IMWG risk classification system allows research teams around the world to use a standardized approach to assess the impact of many exciting new therapies. As Mayo Clinic’s Dr. S. Vincent Rajkumar, a study co-author and IMWG co-chairman, points out: “By pooling resources, databases and samples we can achieve far more than we can alone.” Collective knowledge strongly informs the decision-making process. The IMWG brings together the top myeloma researchers from around the world to, step by step, build our knowledge base to improve outcomes for all myeloma patients.

Expanding our knowledge about the COVID-19 virus

As the world’s experience with COVID-19 will soon be approaching one year, it is important to reflect on key things we have learned so far:

• The science of virus mutations
  We are all familiar with the flu virus and the need for new vaccinations each year. There has been major interest in whether or not the COVID-19 virus mutates (or creates new virus strains) in a similar fashion over time. An important new study (https://www.nature.com/articles/s41586-020-2895-3?) with accelerated publication in the prestigious journal Nature documents that the virus’s spike protein, which binds to cells (ACE-2 receptor) to cause infection, has indeed mutated since early in the pandemic. I have written about this mutation, called D614G (which means that at position #614 there is a G instead of a D), in a previous blog post (https://www.myeloma.org/blog/understanding-second-third-waves-covid-19-we-head-autumn). A number of linked mutations are resulting in what is now the dominant or major virus strain causing infections around the world as part of second and third waves of infection.
  • Increased virus transmission by this new strain
    After a number of very detailed studies the spike mutation research team (a multinational group, again, illustrating the power of collaboration) concludes that the new virus strain D614G is more infectious and more likely to spread easily. However, it does not appear to make patients sicker. The high virus loads in the upper respiratory tract increase the transmission person-to-person in the air
  • Implications of higher air transmission
    This greatly increases the need for and the value of masks in reducing spread. As we head into winter, masks really do matte (https://www.wsj.com/articles/winter-is-coming-time-for-a-mask-mandate-11603659248)r, writes former FDA commissioner Dr. Scott Gottlieb in the Wall St. Journal. Dr. Gottlieb also notes that it is time to consider the quality of masks. A cotton mask offers far less protection than a level 2 or level 3 surgical mask. Thicker is better. If available, an N95 mask definitely offers the best protection. Here is a graphical overview (https://english.elpais.com/society/2020-10-28/a-room-a-bar-and-a-class-how-the-coronavirus-is-spread-through-the-air.html)of the likelihood of infection, as presented in El Pais newspaper, “in three everyday scenarios, based on the safety measures used and the length of exposure.”
• Good news about vaccines
  If COVID-19 has mutated to a new strain, will vaccines still work? The good news is that the D614G strain still triggers the neutralizing antibodies needed to kill the virus. This is a little surprising, but definitely a plus. However, the Nature study researchers mentioned above emphasize the need for very careful monitoring for new virus strains. In the meantime, studies are continuing to move forward, with the Oxford vaccine trial team (https://www.reuters.com/article/health-coronavirus-astrazeneca-vaccine-idUSKBN27B0J1) now closely evaluating older adults, which is so important for myeloma patients. 
• Good news about treatments
  The Regeneron company reported (https://investor.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates/) Wednesday that their REGN-COV2 antibody cocktail significantly reduced virus levels and the need for further medical attention. The findings were based on data from 524 patients enrolled in a phase 2/3 trial. Results have been shared with the FDA and could lead to Emergency Use Authorization in the setting of mild-moderate COVID-19 for patients at high risk of poor outcomes. While an alternate cocktail, developed by Eli Lilly, appears to be ineffective in hospitalized patients, researchers published promising interim results (https://www.nejm.org/doi/full/10.1056/NEJMoa2029849?query-featured_coronavirus=) Wednesday from a trial involving patients with mild and moderate COVID-19.

The bottom line

In the medical field, new science is all we have to develop better treatments and help patients make the best decisions. Let’s keep working together and staying informed to achieve the best we can for everyone. It is tremendously reassuring that overall, myeloma patients have become well informed and, as a result, have been staying remarkably safe despite the many challenges. Let’s try to keep it that way!

PS: Thank you to the nearly 400 support group members who have responded to our survey asking how you are coping during the pandemic. I will report on those answers soon.