The ASH21 Meeting of blood diseases is in the books. What I can share with patients, care partners, and all who are interested is that the myeloma research world is on fire! There are so many new questions for new and veteran researchers, so many creative possible solutions were a part of this annual meeting with a usual attendance of 30,000 health professionals with interests in hematology.
I wanted to share the many advancements being made in the myeloma world – to be able to communicate hope for treatment options and high hopes for a cure for multiple myeloma (MM). There was something new at every level of myeloma treatment — from the newly diagnosed to those who are considered to have relapsed/refractory multiple myeloma (RRMM).
There were an incredible 879 myeloma-related abstracts submitted to the conference — a compelling evidence of increasing interest and progress in this rare cancer by researchers from all over the world. This was a huge increase compared to the number of myeloma abstracts during my first ASH conference 7 years ago in 2014.
The science was sometimes difficult for me to follow, but I knew I would have several opportunities, including leaning on team members to try to understand the mechanisms of new therapies. I knew that I should not get distracted by trying to follow p-values, levels of significance or by understanding the intricacies of targeted therapies. These targeted therapies are moving us closer to precision or personalized medicine. I could gain better understanding of the biology of multiple myeloma and the new strategies to control it.
Some outstanding advances included the seeming omnipresence of the monoclonal antibody, daratumumab, in many therapies – both front line and after three or four therapies. Daratumumab was approved by the FDA in 2015 along with three other drugs. It is interesting to see it taking center stage in combination with various other drugs. The evidence of several clinical trials shows that there may be a change from the current “gold standard” of newly diagnosed myeloma therapy —from three drugs to four drugs.
Population Studies and Biologic Determinants of Myeloma Control
There were several important progress reports on two population studies, one of which is the iStopMM Study (Iceland Screens, Treats, or Prevents Multiple Myeloma) —a part of the Black Swan Research Initiative (BSRI) of the IMF. In this innovative nationwide, randomized clinical trial (RCT), approximately 80,000 adults over 40 years of age who consented to participate were screened for the myeloma precursor monoclonal gammopathy of undetermined significance (MGUS). There were an impressive eight presentations from this clinical trial, including four oral and the remainder poster presentations. One of the significant results is the occurrence of MGUS, expected in the general population as they increase in age. Smoldering multiple myeloma (SMM) incidence was higher than expected. Observations have determined that the use of mass spectrometry versus Serum protein electrophoresis (SPEP) should be used to determine myeloma protein levels.
Because of this unique longitudinal trial, there is genetic sequencing information on all volunteer participants. Finding SMM during screening can allow earlier intervention. The question arises as to whether widespread screening is advisable. The ethics of screening without having an appropriate treatment plan needs to be considered. The results of the studies that come from this trial are highly significant, but come with the limitation of being a homogeneous, virtually all-white population.
Early results from another population clinical trial called the PROMISE Study were presented. In contrast to the demographics of the iStopMM study, the PROMISE Study enrolled myeloma patients 40 and over who self-identified as African American or Black and patients of any race who had a family history of myeloma.
Over 7,200 were screened using SPEP and mass spectroscopy. Overall, MGUS was detected in 10% of volunteers using mass spectroscopy, 6% using SPEP. Some subgroups showed even higher prevalence of MGUS, like African Americans over age 50 with 17% MGUS using mass spectrometry. Clearly, these population studies with different demographics —age, race/ethnicity, geography, genetic sequencing, etc.— will help us unravel the many mysteries of myeloma.
New Approaches to Myeloma Control
Other study results focused on immunotherapy called CAR T therapy, including ABECMA® (idecabtagene vicleucel). On March 26, 2021, the FDA approved idecabtagene vicleucel (also called ide-cel), which targets B cell maturation antigen (BCMA) protein that lives on the myeloma cell. There has been so much work since this therapy was first introduced to reduce major side effects and the expense of CAR T as major barriers for access to this therapy.
The reported outcomes demonstrate remissions that are deeper and last longer, allowing patients and their families a longer period of no treatment. With these advances, there was discussion among some scientists that someday CAR T therapy might replace stem cell transplant as a consideration for earlier therapy than after four prior treatments.
Another major area of research and hope for those who have already been heavily treated for myeloma is the research of bispecific antibodies – an emerging immunotherapy. Bispecific T-cell Engagers (BiTEs) are antibodies that simultaneously target BCMA or other proteins, GPRC5D, and FcRH5 and immune effector cells (like T-cells). Research on all these therapies is ongoing with reports especially on working to decrease side effects like cytokine release syndrome (CRS), cytopenia, and infections.
Social Determinants of Health
I was excited to witness more attention being given to the equally important Social Determinants of Health (SDoH). With all the bench research, and phases I-IV of clinical trials, translating that research to delivery of results to patients and communities must also take center stage. I was encouraged to see the Anti-Racism Studio as a part of the daily agenda at ASH. I believe this heightened awareness of the need for diversity in clinical trials and suggestion from the audience could move the inclusion of diversity in research to a policy level at these scientific sessions. We have to include community engagement in the recruitment of “partners or participants,” not “subjects” to clinical trials. We have to learn from studies like iStopMM and take the clinical trial to the community to remove barriers to participation, such as transportation. We need to consider institutional racism and unconscious bias on the part of providers to be successful in equitable access to care. We should find ways to ensure that all myeloma patients will have access to newly discovered therapies —removing yet another potential barrier to participation. Acknowledging and monitoring for health equity is essential.
I am honored and humbled to be a member of this patient advocate team. It still melts my heart each time I see and hear a researcher-presenter include patients and participants in their acknowledgments. I extend my sincerest appreciation to the IMF and all the sponsors who supported our attendance at this very important annual ASH meeting.
Attending the 63rd American Society of Hematology (ASH) meeting for the first time was an illuminating experience! I feel quite privileged to be a part of the International Myeloma Foundation (IMF) team and to have this educational opportunity. This was an amazing experience and I’m so grateful! Thank you, IMF and my fellow team members!
In my Pre-ASH blog, I organized the SMM abstracts into five (5) categories. To wrap things up, it makes sense to provide highlights from those categories. In some, MGUS research had insightful findings, so those are included as well. Hold on tight — here we go!
Prevalence/demographics: The iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project provides the most compelling data in this category, as they have screened about half of the Icelandic population (40 years and older). They found that 4.9% are monoclonal gammopathy of undetermined significance (MGUS) and .5% are smoldering multiple myeloma (SMM). These numbers suggest that both precursor conditions are more prevalent than previously known. This is, perhaps, not surprising since many MGUS and SMM diagnoses are incidental. The caveat to this data is that Iceland is not very diverse.
The PROMISE study focuses on a Black/African American sample as well as those with a first-degree relative who has a hematologic disorder. They found that the prevalence of MGUS was 10%, higher than expected. This study is ongoing as well, so more results will be forthcoming.
Risk identification/disease progression: Again, iStopMM has interesting findings related to disease progression, as they have followed the screened MGUS individuals (n=3487) for three (3) years. Using a randomized control trial, MGUS screened individuals were placed in one of three arms: (1) not contacted about MGUS (n=1164), (2) followed based on current MGUS guidelines (n=1159), (3) followed with more intensive diagnostics and monitoring (n=1164).
This table shows those who progressed to another diagnosis from each group:
Arm 2 (n=1159)
Arm 3 (n=1164)
Other lymphoproliferative disorder
Treatments/preventing progression: Two strategies currently exist in treating SMM: one is treat to delay progression and the other is treat to cure. These trials are primarily for those with high-risk SMM, although one preliminary result was also reported among those with MGUS and low-risk SMM. MGUS and LRSMM patients are taking daratumumab, and most have demonstrated a response of some degree at this point in time. Longer follow-up is needed to provide a complete picture. The other result was that Grade 3 toxicities occurred in only 5 of 41 patients, while other minor side-effects occurred among more patients.
Findings in the high-risk area are also preliminary, but promising, with longer follow up needed. The following are being studied: (a) the 3-drug combo of ixazomib, lenalidomide, and dexamethasone designed to delay progression, and (b) the combination of KYPROLIS®(carfilzomib), REVLIMID® (lenalidomide), and dexamethasone (KRd) plus stem cell transplant designed to cure.
Disease mechanisms: Frankly, I struggled to understand much of the work in this area. But from my perspective, it seems like various markers are being investigated which can help with earlier disease identification, and I also heard remarks about further stratifying SMM patients into those who may need less frequent follow-up, those who may need closer observation, and those who should probably start treatment. Investigators are looking at things like genomic profiles, mutations, Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) activity, and clonal level markers, among other things. Again, to me this was pretty complex stuff, and I hope to learn more about some of these things in the future. The possibilities do seem quite exciting, however, even to this non-biologist. (Does anyone have a Disease Biology for Dummies book I could borrow?)
COVID-19/vaccine-related information: The iStopMM project again reveals helpful information, as screened MGUS patients had similar rates of SARS-CoV-2 susceptibility and COVID-19 severity, compared to the general public. Regarding SMM patients, one study examining MM patients undergoing treatment also included a small sample of SMM patients in the “no-active-treatment” group. Since the study was focused on treatments, I didn’t see specific statistics regarding the no-active-treatment group, but the figure showed what looked like a slightly depressed response compared to the healthy control group (with no previous COVID-19), especially post dose 1 and within 10 days of receiving dose 2.
To all who have read my blogs, thank you for your interest and attention. I hope that I’ve been able to provide valuable information and insights. I also wish you the very best, in this season of hope.
“Any fool can turn a blind eye but who knows what the ostrich sees in the sand.” – Samuel Barclay Beckett
Colon cancer screening has been shown to reduce the incidence of colon cancer in the general population by identifying premalignant lesions in the colon and treating them. Can screening for elevated blood proteins impact a specific blood cancer? Multiple myeloma (MM) evolves from monoclonal gammopathy of undetermined significance (MGUS) which is completely asymptomatic.
In an attempt to cure or prevent MM, a massive screening study, the Black Swan Research Initiative (BSRI), was undertaken in Iceland. The BSRI was established by International Myeloma Working Group (IMWG) in 2012 to find a cure for MM. The study was given the acronym iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) and was supported by the International Myeloma Foundation (IMF).
The study initiated by Dr. Sigurdur Kristinsson (Professor of Hematology — University of Iceland) involved over 75,000 patients. Everyone over the age of 40 was recruited to participate in the study which included 140,000 individuals in Iceland. Dr. Kristinsson tasked a team of 20 investigators to screen for MGUS, smoldering multiple myeloma (SMM). Those who were diagnosed as either having MGUS or SMM would be randomized in a clinical trial to find an appropriate follow-up to determine if screening can prevent multiple myeloma and its ravaging symptoms. The iStopMM study is a randomized controlled study of identified MGUS or SMM individuals that have been grouped either by clinical monitoring or with lab monitoring to evaluate their progress. A third group will be monitored more aggressively, with more invasive tests to establish a pattern of the development of multiple myeloma.
Another study presented at ASH, known as the PROMISE study, is evaluating screening to reduce the incidence of multiple myeloma and to prevent late complications of bone and kidney disease. The PROMISE study, coordinated by Dr. Irene Ghobrial (Director, Clinical Investigator Research Program, Dana-Farber Cancer Institute — Boston, MA), looks at high-risk individuals. High-risk individuals are defined as being first-degree relatives of patients with blood cancers or African Americans who have 2-3 times greater risk of developing MM. The goal of this study is to evaluate the prevalence of MGUS in this high-risk group. In a cohort of 2,960 high-risk individuals screened, the prevalence of MGUS was found to be significantly increased.
These studies are being conducted to determine if, in the future, watchful monitoring, or offering earlier and more aggressive therapy — based on screening for MGUS, SMM, or early MM — could lead to prevention or a possible cure for multiple myeloma. What one “sees in the sand” by screening may change the course of the disease, like it has been shown for other screening initiatives.
What an amazing time it has been at ASH! #ASH21 #IMFASH21
It was great to see the new trials, updates, and options that are available – or at least soon-to-become available. There was something for almost everyone along their myeloma journey – from monoclonal gammopathy of undetermined significance (MGUS), to smoldering multiple myeloma (SMM), to active myeloma.
How wonderful to see the passion and interest from those within the medical community! I am so thankful for their dedication to find treatment options, protocols, and guidance for those of us with myeloma.
It was also great to get some updates on the vaccines, COVID-19, and myeloma. With new data coming out on many questions that we have had over the past few years, this new information is highly appreciated. For example, it was amazing how the third vaccine shot really made an impact to some of the patients. I truly appreciate all the research being done so that we can try to make the best decisions for ourselves and our families with the information that’s currently available.
I want to thank the IMF for the opportunity to participate in ASH. I also want to thank the IMF and ASH for the virtual component. I feel that I gleaned just as much out of ASH virtually as I would have in-person. I hope that ASH continues to explore the virtual platform for years to come. Virtual attendance makes ASH accessible to everyone – not just to those who are able to travel.
I look forward to sharing these new updates and educational/informational updates with the MM Families Virtual Support Group! I think that to be able to absorb and process all this information, I will go back to the beach and enjoy the blessings of the day— including the hard work and effort that so many dedicated people are making for those with myeloma. Thank you!