Black Swan researchers identify good-risk and poor-risk MRD patients, China’s ‘disruptive’ biotech, and reasons to eat ‘real food’
This week, several reports provide good news for myeloma patients. The Spanish GEM/PETHEMA cooperative study group, supported through the Black Swan Research Initiative, has demonstrated important differences between patients with good- and poor-risk MRD-positive disease in a study published in Leukemia.
Obviously, after definitive treatment such as Velcade, Revlimid, and dexamethasone (VRd) plus autologous stem cell transplant (ASCT), an MRD-negative status is the best. However, if there is residual disease (MRD-positive status), some patients have better outcomes than others, and they can be identified based upon the pattern of myeloma cell surface antigens on the residual cells—what the researchers refer to as “a unique phenotypic profile with independent prognostic value.”
The PETHEMA researchers identified specific patterns of myeloma cell surface antigens that predict for both longer and shorter progression-free and overall survival (PFS and OS). Patterns were based on the high and low expression of certain antigens. The pattern associated with longer PFS and OS includes, among others, antigens that are targets for anti-CD38 monoclonal antibodies, such as Darzalex (daratumumab), and for B cell maturation antigen, which is the target both of experimental antibody therapy and of some of the CAR T cell products now in clinical trials. The pattern associated with poorer PFS includes low expression of CD38.
This information is incredibly useful to guide therapy choices and to assist with further studies.
In separate studies, we are learning important practical details about MRD-positive disease:
1. The MRD-positive myeloma cells can be detected with blood testing—a huge advantage over bone-marrow sampling (a paper has been submitted for publication this year).
2. The genetic patterns of high-risk patients can be assessed. Eight abnormal genes appeared exclusively in the higher-risk patients.
3. Studies can be conducted at the single-cell level to identify whether multiple subclones are involved, rather than just a single, resistant subclone. This has major implications for treatment selection to eliminate residual MRD-positive disease.
All in all, this windfall of positive news moves us several steps forward in our search for better therapies.
China’s “disruptive” approach
As U.S.-based drug makers, such as Celgene, move rapidly forward with their anti-BCMA CAR T-cell therapy programs, conducting trials here and in Europe, Chinese biotech companies are also emerging as industry leaders, with several strategic advantages over U.S. competitors.
With over 10 billion dollars invested in biotechnology, China is entering a phase of true innovation. With this realization, the pharmaceutical giant Johnson & Johnson invested $350 million in China’s Legend Biotech to co-develop a CAR T-cell program called LCAR-B38M, which appears to be uniquely effective for myeloma patients. The story of one U.S. myeloma patient from San Francisco, who travelled to Nanjing, China to receive this CAR T treatment, has been very much in the news. Despite having great anxiety about the potential outcome, this patient, now back in the U.S., has achieved MRD-negative CR (complete remission), and is relieved and doing very well.
What does the future hold? We don’t know. The entry of Chinese biotech companies into the cellular immunotherapy field is viewed as “disruptive” — an approach which can change our perspective about treatment. In China, if a patient fails first (frontline) therapy, he or she can proceed directly to CAR T-cell therapy with the perspective that it is transformative and can produce very long-term CR or even cure. This means that, although expensive, it can be a cost-effective strategy, since it is given once rather than over a course of months or years.
Only time will tell which disruptive approaches to treatment will make a decisive difference for myeloma patients. Achieving cure or even long remissions is a hope, but has not been documented at this point.
From China, we will learn about the impact when CAR T-cell therapy is used earlier in the disease course. And from the U.S., we will learn if one can overcome drug resistance in refractory patients.
Disruptive approaches favored in the Black Swan Research Initiative are to intervene early with decisive, potentially curative therapy, and to look assertively at ways to prevent MGUS (monoclonal gammopathy of undetermined significance), myeloma, and progression of MGUS to myeloma.
Helpful food news
It is clear that eating a healthy diet is a good way to reduce the risk of MGUS and myeloma, as well as delay or prevent progression. The 2018 Environmental Working Group’s Shopper’s Guide to Pesticides in Produce gives excellent advice for those interested in reducing pesticides in their diets. The “clean 15” list of fruits and vegetables is particularly useful. If you cannot find organic produce, this list is the next best thing. And try to avoid anything on the “Dirty Dozen” list, which leads with strawberries.
Another study, described in this New York Times article, reinforces the need to avoid processed foods by highlighting how the sugar trehalose, a softener and stabilizer in many processed foods, distributes bacteria in the gut (intestinal tract) with very negative side effects.
So, once again, Real Food, if feasible, is the healthy answer. Stay tuned as we continue to report on ways forward to help achieve the best outcomes for myeloma patients.
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®.